| 1. |
- Bengtsson, Torbjörn, 1955-, et al.
(författare)
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Leucocyte activation by collagen-stimulated platelets in whole blood
- 2002
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 62:6, s. 451-462
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Tidskriftsartikel (refereegranskat)abstract
- Interaction between vascular cells plays an important role in the initial phases of the inflammatory process, but the mechanisms responsible for cell-cell communication are not fully understood. In this study, activation of leucocytes and platelets in heparinized whole blood was assessed using lumi-aggregometry. This technique enables simultaneous measurement of aggregation and oxygen radical production by monitoring impedance and luminol-amplified chemiluminescence (CL), respectively. Collagen induced aggregation and CL, depending on dose, and markedly enhanced subsequent aggregation and CL-response triggered by the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe). Collagen stimulation of whole blood down- and upregulated the expression of L-selectin and CD11b, respectively. Monoclonal antibodies against sialyl LewisX and P-selectin caused a pronounced inhibition of the oxidative burst, triggered by collagen itself or by a combination of collagen and fMet-Leu-Phe. Furthermore, the Arg-Gly-Asp-Ser(RGDS)-peptide effectively inhibited collagentriggered aggregation and CL, and the subsequent enhancement of the fMet-Leu-Phe-induced responses. This suggests that fibrinogen plays a part in linking platelet GpIIb/IIIa with CD11b on the leucocyte surface. However, neither anti-CD11b nor the PI-peptide (containing the ?-chain motif in fibrinogen that interacts with CD11b) counteracted the stimulatory effects of activated platelets on leucocyte functions. The selectin- and integrin-antagonizing substances were ineffective on the CL-responses induced by fMet-Leu-Phe itself. This study suggests that, through selectin- and integrin-dependent interaction, activated platelets potentiate leucocyte aggregation and oxygen radical production, which might be important for the outcome of inflammatory reactions.
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| 2. |
- Berg, Cecilia, 1976-, et al.
(författare)
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Platelets induce reactive oxygen species-dependent growth of human skin fibroblasts
- 2003
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Ingår i: European Journal of Cell Biology. - : Elsevier BV. - 0171-9335 .- 1618-1298. ; 82:11, s. 565-571
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Tidskriftsartikel (refereegranskat)abstract
- A growing amount of evidence suggests that reactive oxygen species (ROS), such as hydrogen peroxide and superoxide anion, regulate intracellular signalling and have a role in cell proliferation. In the present study, we show that platelets increase the mitogenic rate in human fibroblasts and that this effect was inhibited by the intracellular antioxidant N-acetyl-L-cysteine (NAC) and the NADPH-oxidase inhibitor diphenyleneiodonium chloride (DPI). The mitogenic effects of platelets were mimicked by the platelet factors platelet-derived growth factor BB-isoform (PDGF-BB), transforming growth factor β1 (TGF-β1) and sphingosine-1-phosphate (S1P). The sphingosine kinase inhibitor DL-threo-dihydrosphingosine (DL-dihydro) abrogated the platelet-induced growth, while antibodies directed against PDGF or TGF-β had modest effects. Exposure of fibroblasts to platelets, PDGF-BB, TGF-β1 or S1P caused an extensive intracellular ROS production, measured as changes in dichlorofluorescein fluorescence. This ROS production was totally inhibited by NAC, pyrrolidinethiocarbamate (PDTC), DPI and apocynin. In conclusion, the results presented are indicative of a crucial role of ROS in the platelet-mediated regulation of fibroblast proliferation.
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| 3. |
- Herbertsson, H, et al.
(författare)
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Role of platelets and the arachidonic acid pathway in the regulation of neutrophil oxidase activity
- 2001
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 61:8, s. 641-649
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Tidskriftsartikel (refereegranskat)abstract
- The intercellular mechanisms involved in platelet-mediated regulation of neutrophil function remain incompletely understood. This study investigated the role of the arachidonic acid pathway in the modulation of chemoattractant-induced production of oxygen metabolites, measured as luminol-amplified chemiluminescence (CL). We demonstrate that platelets dose-dependently inhibit the CL response in neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP). Incubation with eicosatetrayonic acid (ETYA), a combined cyclooxygenase and lipooxygenase inhibitor, dramatically decreased the fMLP-induced CL response in neutrophils, an effect that was further enhanced in the presence of platelets. The separate effects of eicosatriyonic acid (ETI) and indomethacin, specific inhibitors of lipoxygenase and cyclooxygenase, respectively, were significantly lower compared to the action of ETYA. On the contrary, impediment of arachidonic acid release with the phospholipase A2 inhibitor arachidonyl trifluoromethyl ketone (ATK) markedly increased the production of oxygen radicals triggered by fMLP. The addition of exogenous arachidonic acid clearly decreased the fMLP-induced CL response in neutrophils, which further strengthens a downregulating effect of arachidonic acid on oxidase activity. This inhibitory action of arachidonic acid, however, was reversed upon co-incubation with platelets. In conclusion, this study suggests that an accumulation of arachidonic acid, following chemotactic peptide stimulation, turns off neutrophil oxidase activity. Furthermore, platelets may support the synthesis of reactive arachidonic acid metabolites, which modulate oxygen radical production in neutrophils.
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| 4. |
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| 5. |
- Kälvegren, Hanna, et al.
(författare)
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Chlamydia pneumoniae binds to platelets and triggers P-selectin expression and aggregation: A causal role in cardiovascular disease?
- 2003
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 23:9, s. 1677-1683
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Tidskriftsartikel (refereegranskat)abstract
- Objective - Evidence linking Chlamydia pneumoniae to atherosclerotic cardiovascular disease is expanding. Platelets are considered to play an essential role in cardiovascular diseases, however, so far platelets have not been associated with an infectious cause of atherosclerosis. This study aims to clarify the interaction between Cpneumoniae and platelets and possibly present a novel mechanism in the pathogenesis of atherosclerosis.Methods and Results - The effects of C pneumoniae on platelet aggregation and secretion were assessed with lumiaggregometry, and the ability of C pneumoniae to bind to platelets and stimulate expression of P-selectin was analyzed with flow cytometry. We found that Cpneumoniae, at a chlamydia:platelet ratio of 1:15, adheres to platelets and triggers P-selectin expression after 1 minute and causes an extensive aggregation and ATP secretion after 20 minutes of incubation. Inhibition of glycoprotein IIb/IIIa with Arg-Gly-Asp-Ser or abciximab markedly reduced C pneumoniae-induced platelet aggregation. Exposure of C pneumoniae to polymyxin B, but not elevated temperature, abolished the stimulatory effects on platelet activation, suggesting that chlamydial lipopolysaccharide has an active role. In contrast, other tested bacteria had no or only moderate effects on platelet functions.Conclusion - Our findings demonstrate a new concept of how C pneumoniae activates platelets and thereby may cause atherosclerosis and thrombotic vascular occlusion.
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| 6. |
- Nimeri, G, et al.
(författare)
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Oxygen radical production in neutrophils interacting with platelets and surface-immobilized plasma proteins : role of tyrosine phosphorylation
- 2003
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Ingår i: Journal of Biomedical Materials Research. - : Wiley. - 0021-9304 .- 1097-4636 .- 1549-3296. ; 67A:2, s. 439-447
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between neutrophil granulocytes and platelets is considered to play an important role in the inflammatory process induced by an implanted foreign material. However, the cellular mechanisms involved remain incompletely understood. We used a luminol-dependent chemiluminescence (CL) technique to analyze the generation of reactive oxygen species (ROS) in human neutrophils interacting with different plasma protein-coated surfaces in the presence or absence of unstimulated or stimulated platelets. The role of tyrosine phosphorylation in the regulation of NADPH oxidase activity was evaluated with quantitative fluorescence microscopy and the specific tyrosine kinase inhibitor genistein. We found that the ROS-production is 2 to 3 times higher in neutrophils on immunoglobulin G (IgG)coated surfaces than in cells interacting with albumin- or fibrinogen-coated surfaces. Incubation with superoxide dismutase and catalase revealed that about 45% of the ROS was released extracellularly on IgG surfaces whereas corresponding values were 90% and 85% in neutrophils interacting with albumin and fibrinogen, respectively. The presence of platelets markedly increased the extracellular generation of ROS, mainly in neutrophils. interacting with IgG- or fibrinogen-coated surfaces whereas the intracellular production was only modestly affected. Quantitative fluorescence microscopy of neutrophils stained with FITC-conjugated anti-phosphotyrosine antibodies showed a correlation between tyrosine phosphorylation, cell spreading, and ROS production. Platelets markedly amplified the anti-phosphotyrosine staining on both fibrinogen- and IgG-coated surfaces whereas the low level of tyrosine phosphorylation in neutrophils on albumin-coated surfaces was not further elevated by platelets. Furthermore, the tyrosine kinase inhibitor genistein inhibited both extra- and intracellular ROS production in neutrophils regardless of the presence of platelets. We demonstrate that plasma protein coating and the presence of platelets are crucial for the inflammatory response of adhering neutrophils and that the oxidative response correlates with the extent of tyrosine phosphorylation of proteins in focal contacts. (C) 2003 Wiley Periodicals, Inc.
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| 7. |
- Nimeri, G, et al.
(författare)
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The influence of plasma proteins and platelets on oxygen radical production and F-actin distribution in neutrophils adhering to polymer surfaces
- 2002
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Ingår i: Biomaterials. - 0142-9612 .- 1878-5905. ; 23:8, s. 1785-1795
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Tidskriftsartikel (refereegranskat)abstract
- It is well known that blood cell interactions with artificial surfaces might have deleterious effects on host tissue, however, the mechanisms involved are far from understood. In this study, neutrophil-platelet interaction on uncoated or protein-coated polymer surfaces was investigated. Cell spreading, reorganization of actin filaments and release of oxygen metabolites (measured as luminol-amplified chemiluminescence) were used as criteria for cell activation on positively charged, hydrophilic 1,2-diaminocyclohexane, and negatively charged, hydrophobic hexamethylene-disiloxane. The model surfaces were made by radio frequency plasma discharge polymerization. Neutrophil contact with the uncoated polymers induced a prolonged generation of oxygen radicals. Precoating of the polymer surfaces with human serum albumin (HSA) or fibrinogen, markedly reduced neutrophil activation, whereas coating with human immunoglobulin G (IgG), a well-known opsonin, resulted in significantly higher levels of cell activation. Consequently, protein coating overruled the activating effects of the polymer surfaces. The presence of unstimulated or thrombin-stimulated platelets markedly increased the reactivity of neutrophils against fibrinogen- and IgG-coated surfaces. However, neutrophils remained relatively unreactive in the presence of platelets on HSA-treated surfaces. Comparison of the different types of surfaces used, reveals a correlation between the degree of cell spreading, reorganization of the actin cytoskeleton and the amount of oxygen radicals produced. Our results suggest that the acute inflammatory reaction on a biomaterial surface is highly dependent on the nature and composition of the first adsorbed protein layer and the extent of platelet activation.
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| 8. |
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| 9. |
- Walldius, Åke, et al.
(författare)
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User-Driven Quality Certification of Workplace Software, the UsersAward Experience
- 2004
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Ingår i: Work with Computing Systems. ; , s. 150-155
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Konferensbidrag (refereegranskat)abstract
- This paper summarizes activities and results from the quality assessment project ITQ, "Quality certification of IT support at work", which was performed by Swedish researchers in close co-operation with trade unions in 1999-2002. The ITQ project is part of a network, UsersAward, which continues to work for the goal to develop and maintain a strategy for good software products on the work floor through strong user influence. A main result from ITQ is the first (2002) version of a user satisfaction based certification method, User Certified 2002, which is described in some detail. Other, parallel activities, large surveys of IT use in work places, user conferences, pilot projects, and a yearly IT Prize contest, are described more briefly. Finally implications and plans for the future, especially international spread of the activities, and further development of the certification process, are described and discussed.
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| 10. |
- Wetterö, Jonas, 1972-, et al.
(författare)
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C1q-independent activation of neutrophils by immunoglobulin M-coated surfaces
- 2001
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Ingår i: Journal of Biomedical Materials Research. - 0021-9304 .- 1097-4636. ; 57:4, s. 550-558
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil granulocytes are known to rapidly adhere and undergo frustrated phagocytosis upon contact with immunoglobulin and/or complement protein opsonized artificial surfaces. In this study, we examined the relation between serum protein deposition and human neutrophil activation on hydrophobic glass and silicon model surfaces that were coated with immunoglobulin G or M (IgG/IgM), both initiators of the classical complement pathway. Protein adsorption from normal human serum (NHS) was quantified with null-ellipsometry combined with antibody techniques. The neutrophil oxygen radical production was registered by luminol-amplified chemiluminescence (CL) and the morphology, as well as changes in the content of filamentous actin (F-actin), were documented by fluorescence microscopy. Complement factor 3 (C3) bound to both IgG- and IgM-coated surfaces, but surprisingly C1q was found only on IgG-coated surfaces. Both immunoglobulins triggered complement dependent neutrophil activation. However, CL and F-actin accumulation were found sensitive to the presence of C1q in the serum only at the IgG-coated surface. We suggest that spontaneously adsorbed IgM activates the complement system and interacts with neutrophils by C1q-independent mechanisms.
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