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| 5. |
- Biglarnia, Ali-Reza, et al.
(författare)
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Desensitization With Antigen-Specific Immunoadsorption Interferes With Complement in ABO-Incompatible Kidney Transplantation
- 2012
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 93:1, s. 87-92
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Complement activation was characterized during and after desensitization treatment in 19 consecutive patients receiving ABO-incompatible (ABOi) living donor kidney transplants to assess the effect of desensitization protocol including antigen-specific immunoadsorption (IA) on complement activation.METHODS:All patients received rituximab- and tacrolimus-based triple treatment. Anti-A/B antibodies were removed by IA. Serial determinations of C3, C3a, the C3a/C3 ratio, and sC5b-9 were carried out between day -30 and postoperative day 30. C1q was measured on day -30 and the day before the transplantation. In two recipients, eluates from immunoadsorbent columns were analyzed for C3a, C1q, and immunoglobulins by western blotting. Same complement analysis was performed in eluate from a control column after in vitro perfusion of AB-plasma.RESULTS:Patient and graft survival were 100% for a median follow-up of 40 months (range, 12-60 months). There were no humoral rejections based on ABO-antigen-antibody interactions. C3a and the C3a/C3 ratio declined with the start of IA treatment, and this decline was maintained postoperatively. C1q declined from day -30 to a lower value on the day before transplantation (P<0.05). In eluates from both patient and control, immunoadsorbent column immunoglobulins together with C3a and C1q were detected.CONCLUSIONS:The current protocol including antigen-specific IA interferes with the complement system; this effect may be partially responsible for the absence of humoral rejection resulting from ABO-antigen-antibody interactions and the excellent outcomes obtained after ABO-incompatible kidney transplantation.
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| 6. |
- Engberg, Anna E., 1982-, et al.
(författare)
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EVALUATION OF THE HEMOCOMPATIBILITY OF NOVEL POLYMERIC MATERIALS
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- When a biomaterial surface comes in contact with blood an immediate adsorption of plasma proteins to the surface will occur, and the cascade systems in the blood, such as the complement, coagulation and contact system, will be activated to various degrees. The intensity of this reaction will determine the hemocompatibility of the materials. Here we present an evaluation of the link between the composition, the physico-chemical properties and the protein adsorption properties of six newly synthesized polymers (P1-P6) and the hemocompatibility.The hemocompatibility of the polymeric surfaces was evaluated in human blood plasma and whole blood. Commercially available polyvinylchloride (PVC) was used as reference material. The hemocompatibility of the polymeric surfaces was evaluated with regard to complement activation (C3a and sC5-9 generation) and coagulation activation (platelet loss and TAT-formation) and cytokine productions (27 analytes in multiplex assay) after contact with whole blood. Contact activation was quantified by analyses of FXIIa-C1INH, FXIa-C1INH, and kallikrein-C1INH complexes.Polymers P2 (p<0.05 for C3a), P3, P5 and P6 showed less complement activation, and polymers P1 and P4 (p<0.05 for platelet loss), as well as P5 and P6 showed less coagulation activation compared with reference PVC. Polymers P1-P3 induced activation of the contact system, P3 being the most potent. Secretion of 17 cytokines including chemokines and growth factors were differentially influenced by the polymers, P1 and P3 being significantly (p<0.05) more compatible for five of the analytes.Collectively these data demonstrate that the composition of the polymers clearly leads to different biological properties as a consequence of distinctive physico-chemical properties and protein adsorption patterns.1
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| 7. |
- Engberg, Anna E., et al.
(författare)
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Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma
- 2015
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 36, s. 55-65
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Tidskriftsartikel (refereegranskat)abstract
- Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-gamma, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard. (C) 2014 Elsevier Ltd. All rights reserved.
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| 11. |
- Hamad, Osama A., 1978-, et al.
(författare)
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Complement activation triggered by chondroitin sulfate released by thrombin receptor-activated platelets
- 2008
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 6:8, s. 1413-1421
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Chondroitin sulfate (CS) is a glycosaminoglycan released by activated platelets. OBJECTIVE: Here we test the hypothesis that CS released by activated platelets can trigger complement activation in the fluid phase. METHODS AND RESULTS: Thrombin receptor-activating peptide (TRAP)-6 was used to activate platelets in platelet-rich plasma and blood, anticoagulated with the thrombin inhibitor lepirudin. TRAP activation induced fluid-phase complement activation, as reflected by the generation of C3a and sC5b-9, which could be attenuated by the C3 inhibitor compstatin. Chondroitinase ABC treatment of supernatants from activated platelets totally inhibited the activation, indicating that platelet-derived CS had initiated the complement activation. Furthermore, addition of purified CS to plasma strongly triggered complement activation. C1q was identified as the recognition molecule, as it bound directly to CS, and CS-triggered complement activation could be restored in C1q-depleted serum by adding purified C1q. TRAP activation of whole blood increased the expression of CD11b on leukocytes and generation of leukocyte-platelet complexes. It was demonstrated that these leukocyte functions were dependent on C3 activation and signaling via C5a, as this expression could be inhibited by compstatin and by a C5aR antagonist. CONCLUSIONS: We conclude that platelets trigger complement activation in the fluid phase by releasing CS, which leads to inflammatory signals mediated by C5a.
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| 12. |
- Hamad, Osama A., 1978-, et al.
(författare)
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Contribution of chondroitin sulfate A to the binding of complement proteins to activated platelets
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:9, s. e12889-
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Tidskriftsartikel (refereegranskat)abstract
- Exposure of chondroitin sulfate A (CS-A) on the surface of activated platelets is well established. The aim of the present study was to investigate to what extent CS-A contributes to the binding of C1q and the complement regulators C1 inhibitor (C1INH), C4b-binding protein (C4BP), and factor H to platelets. Human serum was passed over Sepharose conjugated with CS-A, and bound proteins were identified by Western blotting, and mass spectrometric analysis. C1q was identified as the main protein that specifically bound to CS-A, but C4BP and factor H were also shown to interact. Binding of C1INH was dependent of the presence of C1q and not bound to CS-A from C1q-depleted serum. The specific interactions observed of these proteins with CS-A were subsequently confirmed by surface plasmon resonance analysis using purified proteins. Importantly, C1q, C4BP, and factor H were shown to bind also to activated platelets and this interaction was inhibited by a CS-A-specific monoclonal antibody, thereby linking the binding of C1q, C4BP, and factor H to exposure of CS-A on platelets. CS-A-bound C1q was also shown to amplify the binding of model immune complexes to both microtiter plate-bound CS-A and to activated platelets. In conclusion, this study supports the concept that CS-A contributes to the binding of C1q, C4BP, and factor H to platelets, thereby adding CS-A to the previously reported binding sites for these proteins on the platelet surface. CS-A-bound C1q seems to amplify the binding of immune complexes to activated platelets, suggesting a role for this molecule in immune complex diseases.
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| 13. |
- Hamad, Osama A, et al.
(författare)
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Platelets, Complement, and Contact Activation : Partners in inflammation and thrombosis
- 2012
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Ingår i: Current Topics in Innate Immunity II. - New York, NY : Springer. - 9781461401056 - 9781461401063 ; , s. 185-205
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Konferensbidrag (refereegranskat)abstract
- Platelet activation during thrombotic events is closely associated with complement and contact system activation, which in turn leads to inflammation . Here we review the interactions between activated platelets and the complement and contact activation systems in clotting blood. Chondroitin sulfate A (CS-A), released from alpha granules during platelet activation, is a potent mediator of crosstalk between platelets and the complement system. CS-A activates complement in the fluid phase, generating anaphylatoxins that mediate leukocyte activation. No complement activation seems to occur on the activated platelet surface, but C3 in the form of C3(H2O) is bound to the surfaces of activated platelets . This finding is consistent with the strong expression of membrane-bound complement regulators present at the platelet surface. CS-A exposed on the activated platelets is to a certain amount responsible for recruiting soluble regulators to the surface. Platelet-bound C3(H2O) acts as a ligand for leukocyte CR1 (CD35), potentially enabling platelet–leukocyte interactions. In addition, platelet activation leads to the activation of contact system enzymes, which are specifically inhibited by antithrombin, rather than by C1INH, as is the case when contact activation is induced by material surfaces. Thus, in addition to their traditional role as initiators of secondary hemostasis, platelets also act as mediators and regulators of inflammation in thrombotic events.
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| 14. |
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| 15. |
- Jokiranta, T S, et al.
(författare)
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Complement C3b interactions studied with surface plasmon resonance technique
- 2001
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Ingår i: International Immunopharmacology. - 1567-5769 .- 1878-1705. ; 1:3, s. 495-506
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Tidskriftsartikel (refereegranskat)abstract
- The surface plasmon resonance (SPR) phenomenon is utilized in a number of new real time biosensors. In this study, we have used this technique to study interactions between the central complement component C3b and its multiple ligands by using the Biacore equipment. The SPR technique is particularly suitable for analysis of the alternative complement pathway (AP) because the inherent nature of the latter is to amplify deposition of C3b on various surfaces. C3b was coupled onto the sensor surface and the coupling efficiency was compared under various conditions on both polystyrene and carboxymethylated dextran surfaces. After enzymatic C3b coupling or standard amine C3b coupling, we analyzed and compared the binding of four C3b ligands to the surface: factor B, factor H, C5 and the soluble complement receptor 1 (sCR1, CD35). Binding of each ligand to C3b was detected when C3b had been coupled either enzymatically or using the amine coupling, but the half-lives of the interactions were found to vary depending on the coupling procedure. Factor H binds to C3b via three interaction sites. The target sites are exposed on the C3b, C3c and C3d fragments of C3, respectively. Therefore, we also tested by using the Biacore whether factor B, C5 and sCR1 bind to C3c and/or C3d. It was found that factor B bound to C3d, but not to C3c. On the other hand, both C5 and sCR1 bound to C3c, but not to C3d. In conclusion, this study shows that SPR is a powerful tool in analyzing and mapping the interactions of C3b with its multiple ligands.
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| 16. |
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| 17. |
- Martin, Myriam, et al.
(författare)
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Citrullination of C1-inhibitor as a mechanism of impaired complement regulation in rheumatoid arthritis
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDysregulated complement activation, increased protein citrullination, and production of autoantibodies against citrullinated proteins are hallmarks of rheumatoid arthritis (RA). Citrullination is induced by immune cell-derived peptidyl-Arg deiminases (PADs), which are overactivated in the inflamed synovium. We characterized the effect of PAD2- and PAD4-induced citrullination on the ability of the plasma-derived serpin C1-inhibitor (C1-INH) to inhibit complement and contact system activation. MethodsCitrullination of the C1-INH was confirmed by ELISA and Western blotting using a biotinylated phenylglyoxal probe. C1-INH-mediated inhibition of complement activation was analyzed by C1-esterase activity assay. Downstream inhibition of complement was studied by C4b deposition on heat-aggregated IgGs by ELISA, using pooled normal human serum as a complement source. Inhibition of the contact system was investigated by chromogenic activity assays for factor XIIa, plasma kallikrein, and factor XIa. In addition, autoantibody reactivity to native and citrullinated C1-INH was measured by ELISA in 101 RA patient samples. ResultsC1-INH was efficiently citrullinated by PAD2 and PAD4. Citrullinated C1-INH was not able to bind the serine protease C1s and inhibit its activity. Citrullination of the C1-INH abrogated its ability to dissociate the C1-complex and thus inhibit complement activation. Consequently, citrullinated C1-INH had a decreased capacity to inhibit C4b deposition via the classical and lectin pathways. The inhibitory effect of C1-INH on the contact system components factor XIIa, plasma kallikrein, and factor XIa was also strongly reduced by citrullination. In RA patient samples, autoantibody binding to PAD2- and PAD4-citrullinated C1-INH was detected. Significantly more binding was observed in anti-citrullinated protein antibody (ACPA)-positive than in ACPA-negative samples. ConclusionCitrullination of the C1-INH by recombinant human PAD2 and PAD4 enzymes impaired its ability to inhibit the complement and contact systems in vitro. Citrullination seems to render C1-INH more immunogenic, and citrullinated C1-INH might thus be an additional target of the autoantibody response observed in RA patients.
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| 18. |
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| 19. |
- Nilsson, Bo
(författare)
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Den livsviktiga musiken : delaktighet, hälsa och funktionsmöjligheter
- 2017
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Ingår i: Barnsliga sammanhang. - Kristianstad : Kristianstad University Press. ; :5, s. 65-77
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Det estetiska området har visat sig viktigt för människors möjlighet att uttrycka sig och kommunicera med andra. Förmåga till socialt och kulturellt deltagande har stor betydelse för individens hälsa och välbefinnande. Intresset för att undersöka och utveckla estetiska aktiviteter för barn och unga med olika slag av funktionsnedsättning måste dock anses vara ganska begränsat, något som står i kontrast till den betydelse som ofta uttrycks i skrivelser och styrdokument. I detta kapitel kommer jag att, med exempel från några olika musikprojekt, diskutera delaktighet, hälsa och möjligheter i relation till musikaliska aktiviteter hos barn och unga med funktionsnedsättning.
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| 20. |
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| 21. |
- Nilsson, Bo, et al.
(författare)
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Distinctive expression of neoantigenic C3(D) epitopes on bound C3 following activation and binding to different target surfaces in normal and pathological human sera
- 1989
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Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 26:4, s. 383-390
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Tidskriftsartikel (refereegranskat)abstract
- Binding of C3 to sheep erythrocytes in a serum-free milieu (EAC14oxy2, EAC142) has previously been shown to mimic the antigenic change that occurs upon denaturation of C3 in sodium dodecyl sulphate (SDS), whereby neoantigenic C3(D) epitopes are exposed. The present paper deals with C3 bound to various target surfaces which are known to modulate the functional properties of C3 in different ways. Bound C3 fragments on serum-treated human aggregated gammaglobulin, zymosan, rabbit and sheep erythrocytes, and on circulating immune complexes isolated from sera of patients with rheumatoid arthritis and systemic lupus erythematosus, were shown to be mainly in the iC3b form. By RIAs, employing polyclonal antibodies, the range of C3(D) antigenic epitopes of 125I-labelled SDS denatured C3 expressed by the particle-bound iC3b was monitored. The physiologically bound iC3b on all tested particles expressed wide ranges of C3(D) epitopes and each type of particle-bound C3 exposed its individual range. By competition ELISA specific C3(D)α epitopes were monitored, employing monoclonal antibodies. A distinct difference in the expression of these epitopes was observed in iC3b bound to various test particles in the presence of normal serum and in iC3b present on circulating immune complexes from pathological sera. Considering that the neoantigenic C3(D) epitopes have been shown to be associated with different functions of C3, the distinctive antigenic expression of each type of serum-treated particle might reflect different functional forms of the protein.
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| 22. |
- Nilsson, Bo, et al.
(författare)
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Neoantigens in complement component C3 as detected by monoclonal antibodies. Mapping of the recognized epitopes by synthetic peptides
- 1990
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Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 268:1, s. 55-61
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Tidskriftsartikel (refereegranskat)abstract
- The different fragments of the third complement component, C3, generated upon complement activation/inactivation have the ability to bind to several other complement components and receptors as well as to proteins of foreign origin. These multiple reactivities of C3 fragments are associated with a series of conformational changes occurring in the C3 molecule during its degradation. The conformations acquired by the different C3 fragments are also associated with the exposure of neoantigenic epitopes that are specific for (a) particular fragment(s). In order to study these epitopes and thus the conformational changes occurring in C3, monoclonal antibodies (mAbs) recognizing such epitopes were produced in Balb/c mice after immunization with denatured human C3. Two of the three antibodies (7D84.1 and 7D264.6) presented in this study recognized predominantly surface-bound iC3b, and one mAb (7D323.1) recognized both surface-bound and fluid-phase iC3b. Although none of the mAbs recognized any other fluid-phase C3 fragment, all three antibodies detected micro-titre-plate-fixed C3b and iC3b, but not C3c or C3d. In addition to the reaction with human C3, mAb 7D323.1 also bound to micro-titre-plate-fixed rabbit C3. The epitopes recognized by the three mAbs were further localized by using synthetic peptides that were designed on the basis of the differential binding of the mAbs to the C3 fragments. All three antibodies reacted with C3-(924-965)-peptide, which represents the region of C3 between the kallikrein-cleavage site (923-924) and the elastase-cleavage site (965-966). On the basis of the binding of the mAbs to five different overlapping peptides spanning the region between residues 924 and 965 of the human C3 sequence, and the sequence similarity between human C3 and rabbit C3 within this area, the epitopes recognized by these antibodies are mapped. The contribution of the individual amino acid residues in the formation of the epitopes is discussed.
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| 23. |
- Nilsson, Bo, et al.
(författare)
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Purification and characterization of IgG immunoconglutinins from patients with systemic lupus erythematosus: Implications for a regulatory function
- 1990
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 82:2, s. 262-267
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Tidskriftsartikel (refereegranskat)abstract
- The levels of IgG immunoconglutinins in plasma from patients with rheumatoid arthritis, systemic lupus erythematosus and primary biliary cirrhosis were monitored by ELISA. High levels of IgG immunoconglutinins were found mainly in plasma from patients with systemic lupus erythematosus. These immunoconglutinins bound to microtitre plate-fixed C3, C3b and C3c but poorly to C3d. This binding was inhibited by particle-bound C3b and iC3b but not by the corresponding soluble fragments. Furthermore, Western blot analysis revealed no immunoconglutinin-binding to reduced C3 peptides and no binding was shown to soluble C3 α and β chain by ELISA. IgG immunoconglutinins were purified from three plasma specimens by affinity chromatography on activated thiol sepharose ATS/C3 fragments. Two immunoconglutinin preparations that preferentially recognize ATS-C3b, inhibited C5-converlase function by 50–100% while one immunoconglutinin that recognized ATS-C3d,g had no effect. The two former immunoconglutinins also inhibited all three factor I cleavages in C3α chain but the latter inhibited only the third cleavage. None of the immunoconglutinins affected the binding of complement-coated anti-BSA/BSA complexes to CRI (CD 35) on human erythrocytes, but the two immunoconglutinins that inhibited all factor I cleavages also inhibited the factor I-induced release of anti-BSA/BSA complexes from CRI. The results show that immunoconglutinins recognize specific epitopes on bound C3 fragments and that they are able to modulate C3-mcdiated functions.
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| 24. |
- Nilsson, E.J.C., et al.
(författare)
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Using microdispensing to manufacture a customized cell dish for microbeam irradiation of single, living cells
- 2009
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section B: Beam Interactions with Materials and Atoms. - : Elsevier BV. - 0168-583X. ; 267:7, s. 1199-1205
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Tidskriftsartikel (refereegranskat)abstract
- In this paper is described the preparation of patterned cell dishes to be used in studies of low dose irradiation effects on living cells. Using a droplet microdispenser, an 8 mu m thick polypropylene cell substrate, to which cells do not naturally adhere, was coated in a matrix pattern with the cell adhesive mussel protein Cell-Tak. Cells were shown to adhere and grow on the protein-coated spots, but not on the uncoated parts, providing for guided cell growth. Cultivation of isolated cell colonies provides an opportunity to study how low doses of ionizing radiation affect neighbouring un-irradiated cell colonies. (C) 2009 Elsevier B.V. All rights reserved.
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| 25. |
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| 26. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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An improved method to study complement receptor-mediated function of the fixed macrophage system in vivo
- 1991
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Ingår i: Vox Sanguinis. - : Wiley. - 0042-9007 .- 1423-0410. ; 61:1, s. 47-52
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Tidskriftsartikel (refereegranskat)abstract
- A method to coat unsensitized erythrocytes with fragments of C3 and C4 using autologous serum, in order to study complement receptor-dependent function of the fixed macrophage system, is presented. After incubation with serum under optimal conditions, at least 90% of the cells had C3b/iC3b deposited on the surface, with an average of 20 × 103 molecules per cell. Elimination of the coated cells by the fixed macrophage system was studied in 12 normal subjects. With a dose of 4.5 × 108 red cells injected, 75% of the cells were eliminated with a half-life of approximately 2.4 ± 0.3 min (n = 7). In subjects receiving ten times more cells, there was a rapid decrease in the amount of C3-coated cells, reaching a nadir with 85% remaining for 4–6 min, after which there was a gradual release of cells for another 20 min (n = 5). In absolute numbers, 3 × 108 of labeled cells were eliminated regardless of the dose injected. The coating procedure presented here is simple, does not introduce heterologous blood components and makes it possible to control the amount and the degree of fragmentation of the C3 and C4 deposited on the erythrocyte surface.
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| 27. |
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| 28. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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Defective Fc receptor-mediated clearance in patients with primary biliary cirrhosis
- 1991
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Ingår i: Gastroenterology. - 0016-5085 .- 1528-0012. ; 101:4, s. 1076-1082
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Tidskriftsartikel (refereegranskat)abstract
- Fc receptor-mediated clearance of immunoglobulin G-coated autologous erythrocytes was studied in patients with primary biliary cirrhosis (n = 14), alcoholic liver cirrhosis (n = 5) and healthy reference individuals (n = 14). The mean half-life of the sensitized erythrocytes was significantly prolonged in patients with primary biliary cirrhosis (85 +/- 25 minutes; P less than 0.001) compared with the corresponding value in patients with alcoholic cirrhosis (16 +/- 2 minutes) and healthy reference individuals (20 +/- 5 minutes), respectively. No correlation between clearance rate and age, liver histopathology, or serum levels of bilirubin, aminotransferases, immunoglobulin G, immunoglobulin A, and Clq binding or C3-containing immune complexes was found. The results presented here indicate a profound disturbance of Fc receptor-mediated immune clearance function in patients with primary biliary cirrhosis.
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| 29. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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Development of an immunoassay for the detection of minute amounts of IgG-coated erythrocytes in whole blood: Its application for the assessment of Fc-mediated clearance of anti-D-coated erythrocytes in vivo
- 1989
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Ingår i: Vox Sanguinis. - : Wiley. - 0042-9007 .- 1423-0410. ; 57:3, s. 188-192
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Tidskriftsartikel (refereegranskat)abstract
- A rapid and sensitive immunoassay for the detection of minute quantities of IgG-coated erythrocytes in whole blood was developed. Washed red blood cells were incubated in two steps with anti-human IgG antiserum followed by 125I-labelled protein A. The assay was able to detect amounts of sensitized erythrocytes as small as 0.5 ml of packed erythrocytes in a total blood volume of 5 liters and hematocrit 40%. A linear relation between increasing amounts of IgG-coated red cells in whole blood and the binding of 125I-labelled protein A was obtained. We applied the technique on the assessment of the removal of IgG anti-D-coated erythrocytes from the circulation of test individuals. T1/2 for the elimination of approximately 4 ml packed red cells sensitized with 62 μg of anti-D in 14 normal subjects was 20±5 min (mean±SEM). A splenectomized person did not clear the injected cells from the circulation during the test period of 70 min. If a standard curve was constructed the total blood volume in the test subjects could be calculated. This value correlated well (r = 0.99) with the blood volume calculated from the height and weight of the test individuals.
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| 30. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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Generation of iC3 on the interphase between blood and gas
- 1992
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 35:1, s. 85-91
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Tidskriftsartikel (refereegranskat)abstract
- Earlier studies have shown that C3 can be denatured when blood comes in contact with a polystyrene surface. This study was undertaken to sec if similar denaturation of C3 occurs at the gas plasma interface which is found in all kinds of oxygenator used during cardio-pulmonary operations. An in vitro system consisting of gas bubbling through human blood, serum or plasma was used. The generation of C3a, as an indicator of complement activation, and iC3 and iC3 fragments were monitored. Both C3a and iC3/iC3 fragments levels were increased during bubbling. In contrast to the C3a level, no reduction in iC3/iC3 fragments formation was seen in the presence of EDTA, indicating that il was independent of complement activation. The rate of iC3/iC3 fragments generation was unaffected by the composition of the gas (pure oxygen, pure nitrogen or air), suggesting that the denaturation of C3 indeed occurred at the serum gas interface. C3 and iC3/iC3 fragments were isolated from bubbled EDTA-chelated serum by PEG precipitation and chromatography on FPLC, using a Mono S column and detected by two ELISAs, specific for native C3 and iC3/iC3 fragments. After 240 min approximately 20% of the total amount of C3 consisted of intact iC3 and it was confirmed that this population bound to human erythrocytes.
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| 31. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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Inhibition of factor I by diisopropylfluorophosphate. Evidence of conformational changes in factor I induced by C3b and additional studies on the specificity of factor I
- 1990
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Ingår i: Journal of Immunology. - 0022-1767 .- 1550-6606. ; 144:11, s. 4269-4274
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Tidskriftsartikel (refereegranskat)abstract
- The factor I-mediated cleavage of C3b, using factor H as a cofactor was completely inhibited by diisopropylfluorophosphate (DFP) when factor I and C3b were incubated with DFP before the addition of factor H. Inhibition, although to a lesser degree, was observed when factor H was present during DFP-exposure. No inhibition in factor I activity was seen when factor I and H were incubated with DFP either alone or together. It was also demonstrated that the 38-kDa subunit of factor I bound radiolabeled DFP when factor I and C3b together were exposed to DFP. These observations suggest that factor I interacts with C3b in a manner that exposes its catalytic site to DFP, an interaction that is independent of factor H. The inhibitory effect by DFP on factor I led us to further investigate the factor I cleavage products of iC3b, inasmuch as previous reports were ambiguous as to whether digestion occurs in the presence of DFP. Digestion of C3b bound to activated thiol Sepharose (ATS-C3b) in the presence of factor H at low pH and ionic strength and in serum by complement activation produced C3d,g- like fragments with apparent molecular mass of 41 and 43 kDa. These fragments were shown to have three different N-terminal and two different C-terminal ends. The major fragments had N-terminal sequences starting with Glu933, as shown by sequence determination. Traces of fragments extending beyond this point were also found, shown by Western blot analysis using a panel of mAb previously shown to bind to epitopes exposed within a region of C3 spanning residues 929 to 943, as well as a shorter fragment starting with Glu938. When digestion of C3b is carried out in the presence of DFP, the factor I level necessary for digestion is elevated and may explain how the first two cleavages producing iC3b but not the following giving C3d,g, can occur. The finding of several factor I cleavage sites in the C3d,g region of C3 demonstrates that factor I has a broad specificity, mainly for arginyl bonds. It has also been shown to digest a lysyl bond exposed in ATS- bound C3b.
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| 32. |
- Nilsson Ekdahl, Kristina, et al.
(författare)
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Innate immunity activation on biomaterial surfaces: A mechanistic model and coping strategies
- 2011
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Ingår i: Advanced Drug Delivery Reviews. - : Elsevier BV. - 0169-409X .- 1872-8294. ; 63:12, s. 1042-1050
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Forskningsöversikt (refereegranskat)abstract
- When an artificial biomaterial (e.g., a stent or implantable pump) is exposed to blood, plasma proteins immediately adhere to the surface, creating a new interface between the biomaterial and the blood. The recognition proteins within the complement and contact activation/coagulation cascade systems of the blood will be bound to, or inserted into, this protein film and generate different mediators that will activate polymorphonuclear leukocytes and monocytes, as well as platelets. Under clinical conditions, the ultimate outcome of these processes may be thrombotic and inflammatory reactions, and consequently the composition and conformation of the proteins in the initial layer formed on the surface will to a large extent determine the outcome of a treatment involving the biomaterial, affecting both the functionality of the material and the patient's life quality. This review presents models of biomaterial-induced activation processes and describes various strategies to attenuate potential adverse reactions by conjugating bioactive molecules to surfaces or by introducing nanostructures.
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| 33. |
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| 34. |
- Nilsson, Per H., et al.
(författare)
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The creation of an antithrombotic surface by apyrase immobilization
- 2010
-
Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 31:16, s. 4484-4491
-
Tidskriftsartikel (refereegranskat)abstract
- Blood incompatibility reactions caused by surfaces often involve platelet activation and subsequent platelet-initiated activation of the coagulation and complement cascades. The goal of this study was to immobilize apyrase on a biomaterial surface in order to develop an enzymatically active surface that would have the capacity to inhibit platelet activation by degrading ADP. We were able to immobilize apyrase on a polystyrene surface with preservation of the enzymatic activity. We then analyzed the hemocompatibility of the apyrase surface and of control surfaces by incubation with platelet-rich plasma (PRP) or whole blood. Monitoring of markers of platelet, coagulation, and complement activation and staining of the surfaces revealed decreased levels of platelet and coagulation activation parameters on the apyrase surface. The formation of antithrombin-thrombin and antithrombin-factor XIa complexes and the extent of platelet consumption were significantly lower on the apyrase surface than on any of the control surfaces. No significant differences were seen in complement activation (C3a levels). Staining of the apyrase surface revealed low platelet adherence and no formation of granulocyte platelet complexes. These results demonstrate that it is possible to create an antithrombotic surface targeting the ADP amplification of platelet activation by immobilizing apyrase.
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| 35. |
- Nilsson, Per, et al.
(författare)
-
IMMOBILIZATION OF APYRASE CREATES AN ANTITHROMBOTIC BIOMATERIAL SURFACE
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Blood incompatibility reactions caused by surfaces often involve platelet activation and subsequent platelet-initiated activation of the coagulation and complement cascades. The goal of this proof-of-principle study was to immobilize apyrase on a biomaterial surface in order to develop an enzymatically active surface that would have the capacity to inhibit platelet activation by degradating ADP. We were able to immobilize apyrase on a polystyrene surface with preservation of the enzymatic activity. We then analyzed the hemocompatibility of the apyrase surface and of control surfaces (serum albumin, avidin, polystyrene, and glass) by incubation with platelet-rich plasma (PRP) or whole blood. Monitoring of markers of platelet, coagulation, and complement activation and staining of the surfaces revealed decreased levels of platelet and coagulation activation parameters on the apyrase surface. The level of complex formation between antithrombin and thrombin or factor XIa and the extent of the platelet loss were significantly lower on the apyrase surface than on any of the control surfaces. No significant differences were seen in complement activation (C3a levels). Staining of the apyrase surface revealed low platelet adherence and no formation of granulocyte-platelet complexes. These results demonstrate that it is possible to create an anti-thrombotic surface targeting the ADP amplification of platelet activation by immobilizing apyrase.
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| 36. |
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| 37. |
- Nilsson, Ulf R., et al.
(författare)
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Two conformational forms of target-bound iC3b that distinctively bind complement receptors 1 and 2 and two specific monoclonal antibodies
- 2011
-
Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 116:1, s. 26-33
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. The complement system is an essential part of the immune system of vertebrates. The central event of the complement activation cascade is the sequential proteolytic activation of C3, which is associated with profound alterations in the molecule's structure and conformation and is responsible for triggering most of the biological effects of complement. Material and methods. Here, we have studied the conformation of C3 fragments deposited onto an IgG-coated surface from human serum during complement activation, using a set of unique monoclonal antibodies (mAbs) that are all specific for the C3dg portion of bound iC3b. Results. We were able to identify two conformational forms of target-bound iC3b: the first recognized by mAb 7D18.1, and the second by mAb 7D323.1. The first species of iC3b bound recombinant complement receptor 1 (CR1), while the second bound CR2. Since CR1 and CR2 are expressed by different subsets of leukocytes, this difference in receptor-binding capacity implies that there is a biological difference between the two forms of surface-bound iC3b. Conclusion. We propose that mAbs 7D18.1 and 7D323.1 can act as surrogate markers for CR1 and CR2, respectively, and that they may be useful tools for studying the immune complexes that are generated in various autoimmune diseases.
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| 38. |
- Nilsson, UR, et al.
(författare)
-
Two conformational forms of target bound iC3b which distinctively bind complement receptors 1 and 2 (CR1 and CR2) and two specific monoclonal antibodies.
- 2010
-
Ingår i: Upsala Journal of Medical Sciences, Supplement. - 0300-9726.
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction. The complement system is an essential part of the immune system of vertebrates. The central event of thecomplement activation cascade is the sequential proteolytic activation of C3, which is associated with profound alterations inthe molecule’s structure and conformation and is responsible for triggering most of the biological effects of complement.Material and methods. Here, we have studied the conformation of C3 fragments deposited onto an IgG-coated surface fromhuman serum during complement activation, using a set of unique monoclonal antibodies (mAbs) that are all specific for theC3dg portion of bound iC3b.Results. We were able to identify two conformational forms of target-bound iC3b: the first recognized by mAb 7D18.1, and thesecond by mAb 7D323.1. The first species of iC3b bound recombinant complement receptor 1 (CR1), while the second boundCR2. Since CR1 and CR2 are expressed by different subsets of leukocytes, this difference in receptor-binding capacity impliesthat there is a biological difference between the two forms of surface-bound iC3b.Conclusion. We propose that mAbs 7D18.1 and 7D323.1 can act as surrogate markers for CR1 and CR2, respectively, and thatthey may be useful tools for studying the immune complexes that are generated in various autoimmune diseases.
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| 39. |
- Sandberg, Dick, 1967-, et al.
(författare)
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Utvändiga träfasader : Inverkan av materialval, konstruktion och ytbehandling på beständigheten hos fasader av gran och tall
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Den utvändiga fasaden ska ge byggnaden ett uttryck genom utformning och kulör. Fasaden ska också skydda de isolerande skikten i väggen från yttre påverkan. Dessa funktioner kan uppfyllas av i stort sett alla material. Om trä ska trä vara konkurrenskraftigt måste trämaterialet, fasadkonstruktionen och ytbehandlingssystemet väljas och samverka på ett sådant sätt att fasaden får en lång livslängd med litet och lågt underhåll. Därigenom blir träfasaden ekonomiskt och estetiskt attraktiv för brukaren i vid mening.Denna studie belyser kunskapsfronten för utomhusanvändning av träslagen tall (Pinus sylvestris L.) och gran (Picea abies L. Karst.) ovan mark. Specifikt studeras användning i fasader utifrån aspekterna materialval, fasadkonstruktion, ytbehandling samt återvinning.Marknaden efterfrågar träfasadsystem. De behov som marknadens aktörer, dvs. byggherrar, fastighetsförvaltare, arkitekter, konstruktörer, stomleverantörer, entreprenörer och representanter för småhusindustrin, framhäver kan sammanfattas i följande punkter:Behov av specificerad livslängd och givna tidsintervall för underhåll av träfasader. (Ska vara i nivå med konkurrerande material)Det är önskvärt att leverantören av ett fasadsystem ikläder sig ett långsiktigt ansvar för underhåll.Flexibilitet, leverantören ska kunna byta ut eller renovera fasaden vid behov.Byggkrav, träfasadmaterial måste kunna samverka med andra, speciellt brandklassade, material.Fasadsystem skall vara utseendemässigt attraktivt.Den primära marknaden för nya fasadsystem bör vara flerbostadshus, men inte nödvändigtvis flerbostadshus av trä. Fokus ska ligga på fasadsystemets flexibilitet i arkitektoniskt uttryck och i relation till andra material och system. Nybyggnation är viktigt, men miljonprogrammet, renovering och tillbyggnad (ROT) samt energieffektivisering är också viktiga områden.Den svenska marknaden är liten (idag ca. 70 000 m3 trä för fasader), men bör inledningsvis ändå prioriteras och därefter de nordiska länderna, samt Schweiz, Österrike och Tyskland.I litteraturen beskrivs mer eller mindre välgrundade rekommendationer för att förlänga träfasaders livslängd och öka dess underhålls-intervall. Vissa av rekommendationerna är dock direkt motstridiga.När aspekterna materialval, fasadkonstruktion och ytbehandling studeras finns det många detaljer som har betydelse för träfasadens beständighet. Det är svårt att sära ut de mest väsentliga faktorerna, men utan att ta hänsyn till aspekter som kostnader, tillgång, eller andra av praktiskt karaktär viktiga faktorer kan följande nyckelfaktorer identifieras för en miljöriktig och beständig fasad av tall eller gran:MaterialvalHög andel kärnved, helst uteslutande kärnvedVirket ska ha stående årsringarHanteringen ska utföras så att virket inte får mekaniska skador, får mikrobiella angrepp, eller blir uppfuktat eller nedsmutsat, dvs. snabb och rätt hantering, samt god emballering.Från marken – fasaden ska börja minst 30 cm ovan marken.Ventilation – utforma fasadbeklädnaden så att fukt snabbt kan torka ut. Ventilera utrymmet bakom fasaden vilket är ett enkelt sätt för att möjliggöra detta.Vattenavrinning – inga horisontella ytor.Flexibilitet – ska gälla både konstruktion och arkitektoniskt utförande. Fasadsystem som kan ”hängas på” befintliga byggnader efterfrågas.Förseglat ändträ – försegling av ändträytor för att förhindra fuktupptagning i träet är helt avgörande för trämaterialets livslängd. Spikning kan öppna nya ändträytor och bör därmed utföras omsorgsfullt och med eftertanke.Rundade virkeskanter – ger bättre täckförmåga hos färgen och minskar risk för mekaniska skador på fasadbrädorna.Val av ytbehandling – spelar en nyckelroll för fasadens prestanda. En träfasad ska levereras som en del av ett komplett underhållspaket.Hantering från skog till fasadKonstruktionYtbehandlingFör ytbehandling finns idag många tillämpningar där nanotekniken utnyttjas för att skapa mervärde hos en yta jämfört med vad dagens mer traditionella produkter kan erbjuda. Nanobaserade ytbehandlingsprodukter marknadsförs redan idag och där uppges de göra ytor smuts- och vattenavvisande, förhindra påväxt av alger, svamp och mossa, förbättra UV- och temperaturresistensen och kulörbeständigheten, förbättra rep- och nötningståligheten, samt ha antigraffiti egenskaper etc. De flesta produkterna är dock nya och för en del finns därför frågetecken vad gäller t.ex. långtidsprestanda och teknisk livslängd, underhållbarhet och därmed sammanhängande ekonomi sett ur ett livscykelperspektiv för den produkt eller system där ytbehandlingen utgör bara en del.En kostnadsanalys som genomförts i studien gör bedömningen att nya nanoteknikbaserade ytbehandlingssystem skulle kunna ge som mest en reduktion av underhållskostnaderna med 15 %. Antagandet är då att fasadrengöring behöver göras vart femte eller sjunde år då traditionella målningssystem används.Återvunnet trä från träfasader definieras enligt Svensk standard som trädbränsle och benämns generellt för returträ eller när materialet är i finfördelad form för returflis.Ett stort problem med att återvinna energin från returträ är att en del av materialet är behandlat på något sätt, t.ex. impregnerat med träskyddsmedel, ytbehandlat eller innehåller andra konstruktionsdelar av t.ex. plast eller metall. Returflis är ett utmärkt bränsle för energiåtervinning förutsatt att anläggningen har tillräcklig rökgasrening och att askan hanteras på ett korrekt sätt. Ett problem idag är vad som ska ske med förorenad askan då den klassas som farligt avfall och därmed inte kan återföras till skogen. Om halterna av tungmetaller inte är för höga kan askan användas som täck- och fyllmaterial annars måste askan gå till deponi.En bättre källsortering och översyn av regelverk skulle dessutom kunna leda till att det renare returträet skulle kunna eldas i konventionella biobränslepannor medan den förorenade andelen då skulle eldas separat.
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| 40. |
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| 41. |
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| 42. |
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| 43. |
- Adler, Anna, et al.
(författare)
-
A Robust Method to Store Complement C3 With Superior Ability to Maintain the Native Structure and Function of the Protein
- 2022
-
Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Complement components have a reputation to be very labile. One of the reasons for this is the spontaneous hydrolysis of the internal thioester that is found in both C3 and C4 (but not in C5). Despite the fact that approximate to 20,000 papers have been published on human C3 there is still no reliable method to store the protein without generating C3(H2O), a fact that may have affected studies of the conformation and function of C3, including recent studies on intracellular C3(H2O). The aim of this work was to define the conditions for storage of native C3 and to introduce a robust method that makes C3 almost resistant to the generation of C3(H2O). Here, we precipitated native C3 at the isoelectric point in low ionic strength buffer before freezing the protein at -80 degrees C. The formation of C3(H2O) was determined using cation exchange chromatography and the hemolytic activity of the different C3 preparations was determined using a hemolytic assay for the classical pathway. We show that freezing native C3 in the precipitated form is the best method to avoid loss of function and generation of C3(H2O). By contrast, the most efficient way to consistently generate C3(H2O) was to incubate native C3 in a buffer at pH 11.0. We conclude that we have defined the optimal storage conditions for storing and maintaining the function of native C3 without generating C3(H2O) and also the conditions for consistently generating C3(H2O).
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| 44. |
- Adler, Anna, et al.
(författare)
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Effect of liposome surface modification with water-soluble phospholipid polymer chain-conjugated lipids on interaction with human plasma proteins
- 2022
-
Ingår i: Journal of materials chemistry. B. - : Royal Society of Chemistry. - 2050-750X .- 2050-7518. ; 10:14, s. 2512-2522
-
Tidskriftsartikel (refereegranskat)abstract
- Alternative liposome surface coatings for PEGylation to evade the immune system, particularly the complement system, have garnered significant interest. We previously reported poly(2-methacryloyloxyethyl phosphorylcholine) (MPC)-based lipids (PMPC-lipids) and investigated the surface modification of liposomes. In this study, we synthesize PMPC-lipids with polymerization degrees of 10 (MPC10-lipid), 20 (MPC20-lipid), 50 (MPC50-lipid), and 100 (MPC100-lipid), and coated liposomes with 1, 5, or 10 mol% PMPC-lipids (PMPC-liposomes). Non-modified and PEGylated liposomes are used as controls. We investigate the liposome size, surface charge, polydispersity index, and adsorption of plasma proteins to the liposomes post incubation in human plasma containing N,N,N′,N′-ethylenediamine tetraacetic acid (EDTA) or lepirudin by some methods such as sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), western blotting, and automated capillary western blot, with emphasis on the binding of complement protein C3. It is shown that the coating of liposome PMPC-lipids can suppress protein adsorption more effectively with an increase in the molecular weight and molar ratio (1-10 mol%). Apolipoprotein A-I is detected on PMPC-liposomes with a higher molecular weight and higher molar ratio of PMPC-lipids, whereas α2-macroglobulin is detected on non-modified, PEGylated, and PMPC-liposomes with a shorter polymer chain. In addition, a correlation is shown among the PMPC molecular weight, molar ratio, and C3 binding. The MPC10-lipid cannot inhibit C3 binding efficiently, whereas surface modifications with 10 mol% MPC20-lipid and 5 mol% and 10 mol% MPC50-lipid suppress both total protein and C3 binding. Hence, liposome modification with PMPC-lipids can be a possible strategy for avoiding complement activation.
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| 45. |
- Adler, Anna, et al.
(författare)
-
Effect of liposome surface modification with water-soluble phospholipid polymer chain-conjugated lipids on interaction with human plasma proteins
- 2022
-
Ingår i: Journal of materials chemistry. B. - : Royal Society of Chemistry (RSC). - 2050-750X .- 2050-7518. ; 10:14, s. 2512-2522
-
Tidskriftsartikel (refereegranskat)abstract
- Alternative liposome surface coatings for PEGylation to evade the immune system, particularly the complement system, have garnered significant interest. We previously reported poly(2-methacryloyloxyethyl phosphorylcholine) (MPC)-based lipids (PMPC-lipids) and investigated the surface modification of liposomes. In this study, we synthesize PMPC-lipids with polymerization degrees of 10 (MPC10-lipid), 20 (MPC20-lipid), 50 (MPC50-lipid), and 100 (MPC100-lipid), and coated liposomes with 1, 5, or 10 mol% PMPC-lipids (PMPC-liposomes). Non-modified and PEGylated liposomes are used as controls. We investigate the liposome size, surface charge, polydispersity index, and adsorption of plasma proteins to the liposomes post incubation in human plasma containing N,N,N ',N '-ethylenediamine tetraacetic acid (EDTA) or lepirudin by some methods such as sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), western blotting, and automated capillary western blot, with emphasis on the binding of complement protein C3. It is shown that the coating of liposome PMPC-lipids can suppress protein adsorption more effectively with an increase in the molecular weight and molar ratio (1-10 mol%). Apolipoprotein A-I is detected on PMPC-liposomes with a higher molecular weight and higher molar ratio of PMPC-lipids, whereas alpha(2)-macroglobulin is detected on non-modified, PEGylated, and PMPC-liposomes with a shorter polymer chain. In addition, a correlation is shown among the PMPC molecular weight, molar ratio, and C3 binding. The MPC10-lipid cannot inhibit C3 binding efficiently, whereas surface modifications with 10 mol% MPC20-lipid and 5 mol% and 10 mol% MPC50-lipid suppress both total protein and C3 binding. Hence, liposome modification with PMPC-lipids can be a possible strategy for avoiding complement activation.
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| 46. |
- Adler, Anna, et al.
(författare)
-
Regulation of the innate immune system by fragmented heparin-conjugated lipids on lipid bilayered membranes in vitro
- 2023
-
Ingår i: Journal of materials chemistry. B. - : Royal Society of Chemistry. - 2050-750X .- 2050-7518. ; 11:46, s. 11121-11134
-
Tidskriftsartikel (refereegranskat)abstract
- Surface modification with heparin is a powerful biomaterial coating strategy that protects against innate immunity activation since heparin is a part of the proteoglycan heparan sulfate on cell surfaces in the body. We studied the heparinization of cellular and material surfaces via lipid conjugation to a heparin-binding peptide. In the present study, we synthesized fragmented heparin (fHep)-conjugated phospholipids and studied their regulation of the innate immune system on a lipid bilayered surface using liposomes. Liposomes have versatile applications, such as drug-delivery systems, due to their ability to carry a wide range of molecules. Owing to their morphological similarity to cell membranes, they can also be used to mimic a simple cell-membrane to study protein-lipid interactions. We investigated the interaction of complement-regulators, factor H and C4b-binding protein (C4BP), as well as the coagulation inhibitor antithrombin (AT), with fHep-lipids on the liposomal surface. Herein, we studied the ability of fHep-lipids to recruit factor H, C4BP, and AT using a quartz crystal microbalance with dissipation monitoring. With dynamic light scattering, we demonstrated that liposomes could be modified with fHep-lipids and were stable up to 60 days at 4 degree celsius. Using a capillary western blot-based method (Wes), we showed that fHep-liposomes could recruit factor H in a model system using purified proteins and assist in the degradation of the active complement protein C3b to iC3b. Furthermore, we found that fHep-liposomes could recruit factor H and AT from human plasma. Therefore, the use of fHep-lipids could be a potential coating for liposomes and cell surfaces to regulate the immune system on the lipid surface.
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| 47. |
- Adler, Anna, et al.
(författare)
-
Synthesis of poly(2-methacryloyloxyethyl phosphorylcholine)-conjugated lipids and their characterization and surface properties of modified liposomes for protein interactions
- 2021
-
Ingår i: Biomaterials Science. - : Royal Society of Chemistry. - 2047-4830 .- 2047-4849. ; 9:17, s. 5854-5867
-
Tidskriftsartikel (refereegranskat)abstract
- Poly(ethylene glycol) (PEG) is frequently used for liposomal surface modification. However, as PEGylated liposomes are cleared rapidly from circulation upon repeated injections, substitutes of PEG are being sought. We focused on a water-soluble polymer composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) units, and synthesized poly(MPC) (PMPC)-conjugated lipid (PMPC-lipid) with degrees of MPC polymerization ranging from 10 to 100 (calculated molecular weight: 3 to 30 kDa). In addition, lipids with three different alkyl chains, myristoyl, palmitoyl, and stearoyl, were applied for liposomal surface coating. We studied the interactions of PMPC-lipids with plasma albumin, human complement protein C3 and fibrinogen using a quartz crystal microbalance with energy dissipation, and found that adsorption of albumin, C3 and fibrinogen could be suppressed by coating with PMPC-lipids. In particular, the effect was more pronounced for PMPC chains with higher molecular weight. We evaluated the size, polydispersity index, surface charge, and membrane fluidity of the PMPC-lipid-modified liposomes. We found that the effect of the coating on the dispersion stability was maintained over a long period (98 days). Furthermore, we also demonstrated that the anti-PEG antibody did not interact with PMPC-lipids. Thus, our findings suggest that PMPC-lipids can be used for liposomal coating.
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| 48. |
- Aeinehband, Shahin, et al.
(författare)
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Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis
- 2015
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
-
Tidskriftsartikel (refereegranskat)abstract
- Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genomewide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE), an enzyme hydrolyzing acetylcholine (ACh), a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL), a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE) and BuChE, in cerebrospinal fluid (CSF) from patients with MS (n = 48) and non-inflammatory controls (n = 18). C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with >= 9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone.
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| 49. |
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| 50. |
- Alves Dias, Joana, et al.
(författare)
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Low-grade inflammation, oxidative stress and risk of invasive post-menopausal breast cancer - A nested case-control study from the Malmö diet and cancer cohort
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Although cancer promotes inflammation, the role of inflammation in tumor-genesis is less well established. The aim was to examine if low-grade inflammation is related to post-menopausal breast cancer risk, and if obesity modifies this association. Methods; In the Malmo Diet and Cancer cohort, a nested case-control study was defined among 8,513 women free of cancer and aged 55.73 years at baseline (1991.96); 459 were diagnosed with invasive breast cancer during follow-up (until December 31st, 2010). In laboratory analyses of blood from 446 cases, and 885 controls (matched on age and date of blood sampling) we examined systemic inflammation markers: oxidized (ox)-LDL, interleukin (IL)- 1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, white blood cells, lymphocytes and neutrophils. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer risk was calculated using multivariable conditional logistic regression. Results: Inverse associations with breast cancer were seen in fully-adjusted models, for 2nd and 3rd tertiles of ox-LDL, OR (95% CI): 0.65 (0.47.0.90), 0.63 (0.45.0.89) respectively, p-trend = 0.01; and for the 3rd tertile of TNF-α, 0.65 (0.43.0.99), p-trend = 0.04. In contrast, those in the highest IL-1β category had higher risk, 1.71 (1.05.2.79), p-trend = 0.01. Obesity did not modify associations between inflammation biomarkers and breast cancer. Conclusion; Our study does not suggest that low-grade inflammation increase the risk of post-menopausal breast cancer.
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