Plasma gelsolin facilitates interaction between β2 glycoprotein I and α5β1 integrin
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概要
- 論文の詳細を見る
Antiphospholipid syndrome (APS) is characterized by thrombosis and the presence of antiphospholipid antibodies (aPL) that directly recognizes plasma β2 glycoprotein I (β2GPI). Tissue factor (TF), the major initiator of the extrinsic coagulation system, is induced on monocytes by aPL in vitro, explaining in part the pathophysiology in APS. We previously reported that the mitogen-activated protein kinase (MAPK) pathway plays an important role in aPL-induced TF expression on monocytes. In this study, we identified plasma gelsolin as a protein associated with β2GPI by using immunoaffinity chromatography and mass spectrometric analysis. An in vivo binding assay showed that endogenous β2GPI interacts with plasma gelsolin, which binds to integrin α5β1 through fibronectin. The tethering of β2GPI to monoclonal anti-β2GPI autoantibody on the cell surface was enhanced in the presence of plasma gelsolin. Immunoblot analysis demonstrated that p38 MAPK protein was phosphorylated by monoclonal anti-β2GPI antibody treatment, and its phosphorylation was attenuated in the presence of anti-integrin α5β1 antibody. Furthermore, focal adhesion kinase (FAK), a downstream molecule of the fibronectin-integrin signalling pathway, was phosphorylated by anti-β2GPI antibody treatment. These results indicate that molecules including gelsolin and integrin are involved in the anti-β2GPI antibody-induced MAPK pathway on monocytes and that integrin is a possible therapeutic target to modify a prothrombotic state in patients with APS.
著者
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ATSUMI Tatsuya
Department of Medicine II, Hokkaido University Graduate School of Medicine
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Koike Takao
Hokkaido Univ. Graduate School Of Medicine Sapporo Jpn
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HORITA Tetsuya
Department of Medicine II, Hokkaido University Graduate School of Medicine
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YASUDA Shinsuke
Department of Medicine II, Hokkaido University Graduate School of Medicine
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Atsumi Toru
Laboratory Of Developmental Immunology And The Core Research For Evolutional Science And Technology
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Horita Tetsuya
Department Of Medicine Ii Hokkaido University Graduate School Of Medicine
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Yasuda Shinsuke
Department Of Medicine Ii Hokkaido University Graduate School Of Medicine
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Koike Takao
Department of Medicine II, Hokkaido University Graduate School of Medicine
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