| 1. |
- Zaher, Yumna, 1991-, et al.
(författare)
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Protein based nanomedicine : Promising therapeutic modalities against inflammatory disorders
- 2022
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Ingår i: Nanoselect. - : John Wiley & Sons. - 2688-4011. ; 3:4, s. 733-750
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Tidskriftsartikel (refereegranskat)abstract
- The safe and targeted delivery of pharmaceutical formulations has relied exten-sively on synthetic chemistry and other physicochemical approaches. Theresearch paradigm is now especially changing towards green (or environmentallyfriendly) approaches, and several biopolymer-based nanocarriers are marked asemerging nanomedicine tools. These have been developed to overcome problemswith conventional drug carriers, which induce severe side effects, especially dueto non-specificity with detrimental effects on non-targeted normal healthy cells.In addition, the phagocytosis of classic nanoparticles (NPs) and their degrada-tion associated with the formation of oxygen radicals by the immune systemare significant barriers for drug delivery. In this regard, protein nanocarriersappear as a promising approach to escape unwanted immune reactions. More-over, these protein-based NPs are generally non-toxic, biodegradable, and evencost-effective. As a less appreciated advantage, the surface properties of proteinsare easily modified. There are, however, several challenges and limiting choicesto make when choosing the type of modification to enable effective drug delivery.Here, we shed light on the role of protein nanocarriers for enhancing the bioavail-ability of different anti-inflammatory drugs, including better macrophage target-ing and overcoming biological barriers. This insight helps one to understandtheir broad utility in the treatment of inflammatory diseases and bridges thegap between naturaltherapeutic products and nanotechnology-based deliveryapproaches, creating perhaps an optimal blend to meet some of our most per-sistent healthcare problems.
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| 2. |
- Gjelstrup, Louise Carstensen, et al.
(författare)
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The role of higher-order protein structure in supporting binding by heteroclitic monoclonal antibodies: The monoclonal antibody KIM185 to CD18 also binds C4-binding protein
- 2011
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Ingår i: Molecular Immunology. - : Elsevier BV. - 1872-9142 .- 0161-5890. ; 49:1-2, s. 38-47
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Tidskriftsartikel (refereegranskat)abstract
- Heteroclitic monoclonal antibodies are characterized by the ability to bind multiple epitopes with little or no similarity. Such antibodies have been reported earlier, but insight into to the molecular basis of this propensity is limited. Here we report that the KIM185 antibody to human CD18 reacts with the plasma protein C4b-binding protein (C4BP). This was revealed during affinity purification procedures where human serum was incubated with surfaces coated with monoclonal antibodies to CD18. Other monoclonal antibodies to CD18 (KIM127 and TS1/18) showed no such interaction with C4BP. We constructed a sandwich-type time-resolved immunofluorometric assay using KIM185 both as capture and developing antibody. By use of proteolytic fragments of KIM185 and recombinant deletion mutants of C4BP the interaction sites were mapped to the variable region of KIM185 and the oligomerization domain of C4BP, respectively. C4BP is a large oligomeric plasma protein that binds activated complement factor C4b and other endogenous ligands as well as microorganisms. By use of the recent crystallographic data on the structure of CD11c/CD18 and prediction of the secondary structure of the C4BP oligomerization domain, we show that epitopes bound by KIM185 in these proteins are unlikely to share any major structural similarity. However, both antigens may form oligomers that would enable avid binding by the antibody. Our report points to the astonishing ability of heteroclitic antibodies to accommodate the binding of multiple proteins with no or little structural similarity within the confined space of the variable regions. (C) 2011 Elsevier Ltd. All rights reserved.
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| 3. |
- Nielsen, Morten Aagaard, et al.
(författare)
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Galectin-3 Decreases 4-1BBL Bioactivity by Crosslinking Soluble and Membrane Expressed 4-1BB
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- 4-1BB is a T cell costimulatory receptor and a member of the tumor necrosis factor receptor superfamily. Here, we show that Galectin-3 (Gal-3) decreases the cellular response to its ligand (4-1BBL). Gal-3 binds to both soluble 4-1BB (s4-1BB) and membrane-bound 4-1BB (mem4-1BB), without blocking co-binding of 4-1BBL. In plasma, we detected complexes composed of 4-1BB and Gal-3 larger than 100 nm in size; these complexes were reduced in synovial fluid from rheumatoid arthritis. Both activated 4-1BB+ T cells and 4-1BB-transfected HEK293 cells depleted these complexes from plasma, followed by increased expression of 4-1BB and Gal-3 on the cell surface. The increase was accompanied by a 4-fold decrease in TNFα production by the 4-1BBhighGal-3+ T cells, after exposure to 4-1BB/Gal-3 complexes. In RA patients, complexes containing 4-1BB/Gal-3 were dramatically reduced in both plasma and SF compared with healthy plasma. These results support that Gal-3 binds to 4-1BB without blocking the co-binding of 4-1BBL. Instead, Gal-3 leads to formation of large soluble 4-1BB/Gal-3 complexes that attach to mem4-1BB on the cell surfaces, resulting in suppression of 4-1BBL’s bioactivity.
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| 4. |
- Zhang, Ming, et al.
(författare)
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Identification of the target self-antigens in reperfusion injury.
- 2006
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 203:1, s. 141-52
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Tidskriftsartikel (refereegranskat)abstract
- Reperfusion injury (RI), a potential life-threatening disorder, represents an acute inflammatory response after periods of ischemia resulting from myocardial infarction, stroke, surgery, or trauma. The recent identification of a monoclonal natural IgM that initiates RI led to the identification of nonmuscle myosin heavy chain type II A and C as the self-targets in two different tissues. These results identify a novel pathway in which the innate response to a highly conserved self-antigen expressed as a result of hypoxic stress results in tissue destruction.
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