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| Item Type: | Article |
|---|---|
| Title: | Glatiramer acetate (Copaxone) modulates platelet activation and inhibits thrombin-induced calcium influx: Possible role of copaxone in targeting platelets during autoimmune neuroinflammation |
| Creators Name: | Starossom, S.C., Veremeyko, T., Dukhinova, M., Yung, A.W.Y. and Ponomarev, E.D. |
| Abstract: | BACKGROUND: Glatiramer acetate (GA, Copaxone, Copolymer-1) is an FDA approved drug for the treatment of MS and it is very effective in suppressing neuroinflammation in experimental autoimmune encephalitis (EAE), an animal model of MS. Although this drug was designed to inhibit pathogenic T cells, the exact mechanism of EAE/MS suppression by GA is still not well understood. Previously we presented evidence that platelets become activated and promote neuroinflammation in EAE, suggesting a possible pathogenic role of platelets in MS and EAE. We hypothesized that GA could inhibit neuroinflammation by affecting not only immune cells but also platelets. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the effect of GA on the activation of human platelets in vitro: calcium influx, platelet aggregation and expression of activation markers. Our results in human platelets were confirmed by in-vitro and in-vivo studies of modulation of functions of platelets in mouse model. We found that GA inhibited thrombin-induced calcium influx in human and mouse platelets. GA also decreased thrombin-induced CD31, CD62P, CD63, and active form of αIIbβ3 integrin surface expression and formation of platelet aggregates for both mouse and human platelets, and prolonged the bleeding time in mice by 2.7-fold. In addition, we found that GA decreased the extent of macrophage activation induced by co-culture of macrophages with platelets. CONCLUSIONS: GA inhibited the activation of platelets, which suggests a new mechanism of GA action in suppression of EAE/MS by targeting platelets and possibly preventing their interaction with immune cells such as macrophages. Furthermore, the reduction in platelet activation by GA may have additional cardiovascular benefits to prevent thrombosis. |
| Keywords: | B7-2 Antigen, Bleeding Time, Blood Platelets, Calcium, Coculture Techniques, Cultured Cells, Experimental Autoimmune Encephalomyelitis, Glatiramer Acetate, Histocompatibility Antigens Class II, Immunologic Adjuvants, Inbred C57BL Mice, Ion Transport, Multiple Sclerosis, Peptides, Peritoneal Macrophages, Platelet Activation, Platelet Endothelial Cell Adhesion Molecule-1, Platelet Glycoprotein GPIIb-IIIa Complex, P-Selectin, Thrombin, Animals, Mice |
| Source: | PLoS ONE |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Volume: | 9 |
| Number: | 5 |
| Page Range: | e96256 |
| Date: | 2 May 2014 |
| Official Publication: | https://doi.org/10.1371/journal.pone.0096256 |
| PubMed: | View item in PubMed |
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