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Plasma gelsolin facilitates interaction between β2 glycoprotein I and α5β1 integrin
Miyuki Bohgaki1, Masaki Matsumoto, Tatsuya Atsumi
1Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Journal of Cellular and Molecular Medicine
|October 21, 2009
Summary
Antiphospholipid syndrome involves antiphospholipid antibodies binding to β(2)-glycoprotein I. This study reveals gelsolin and integrin mediate the antibody-induced MAPK pathway in monocytes, suggesting integrin as a therapeutic target for thrombosis.
Area of Science:
- Immunology
- Hematology
- Cell Biology
Background:
- Antiphospholipid syndrome (APS) is linked to thrombosis and antiphospholipid antibodies (aPL) targeting β(2)-glycoprotein I (β(2) GPI).
- Monocyte tissue factor (TF) induction by aPL contributes to APS pathophysiology.
- The mitogen-activated protein kinase (MAPK) pathway is implicated in aPL-induced TF expression.
Purpose of the Study:
- To identify proteins interacting with β(2) GPI in APS.
- To elucidate the role of β(2) GPI-associated proteins in the MAPK signaling pathway.
- To explore potential therapeutic targets for APS-related prothrombotic states.
Main Methods:
- Immunoaffinity chromatography and mass spectrometry to identify β(2) GPI-binding proteins.
- In vivo binding assays to confirm protein interactions.
- Western blot analysis to assess MAPK pathway activation (p38 MAPK, focal adhesion kinase) and the effect of blocking antibodies.
Main Results:
- Plasma gelsolin was identified as a β(2) GPI-associated protein.
- Endogenous β(2) GPI interacts with gelsolin, which binds to integrin α(5)β(1) via fibronectin.
- Monoclonal anti-β(2) GPI antibodies induce p38 MAPK and focal adhesion kinase phosphorylation, an effect modulated by anti-integrin α(5)β(1) antibodies.
Conclusions:
- Gelsolin and integrin α(5)β(1) are involved in the anti-β(2) GPI antibody-induced MAPK pathway in monocytes.
- The fibronectin-integrin signaling pathway plays a role in mediating prothrombotic effects in APS.
- Integrin α(5)β(1) represents a potential therapeutic target for managing thrombosis in APS patients.
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