Plasma gelsolin facilitates interaction between β2 glycoprotein I and α5β1 integrin

Miyuki Bohgaki, Masaki Matsumoto, Tatsuya Atsumi, Takeshi Kondo, Shinsuke Yasuda, Tetsuya Horita, Keiichi I. Nakayama, Fumihiko Okumura, Shigetsugu Hatakeyama, Takao Koike

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

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 a5β1 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 a5β1 antibody. Furthermore, focal adhesion kinase, 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.

Original languageEnglish
Pages (from-to)141-151
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume15
Issue number1
DOIs
Publication statusPublished - Jan 2011

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Cell Biology

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