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Plasma gelsolin facilitates interaction between β2 glycoprotein I and α5β1 integrin

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Title: Plasma gelsolin facilitates interaction between β2 glycoprotein I and α5β1 integrin
Authors: Bohgaki, Miyuki Browse this author
Matsumoto, Masaki Browse this author
Atsumi, Tatsuya Browse this author
Kondo, Takeshi Browse this author
Yasuda, Shinsuke Browse this author
Horita, Tetsuya Browse this author
Nakayama, Keiichi I. Browse this author
Okumura, Fumihiko Browse this author
Hatakeyama, Shigetsugu Browse this author →KAKEN DB
Koike, Takao Browse this author →KAKEN DB
Keywords: β2GPI
gelsolin
integrin
TF
APS
Issue Date: Jan-2011
Publisher: Blackwell Publishing
Journal Title: Journal of Cellular and Molecular Medicine
Volume: 15
Issue: 1
Start Page: 141
End Page: 151
Publisher DOI: 10.1111/j.1582-4934.2009.00940.x
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 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.
Rights: The definitive version is available at www.blackwell-synergy.com
Type: article (author version)
URI: http://hdl.handle.net/2115/47950
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 畠山 鎮次

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