Plasma gelsolin facilitates interaction between β2 glycoprotein I and α5β1 integrin.
Plasma gelsolin facilitates interaction between β2 glycoprotein I and α5β1 integrin.
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DOI：
10.1111/j.1582-4934.2009.00940.x
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发表时间：
2011-01
影响因子：
5.3
通讯作者：
Koike T
中科院分区：
文献类型：
--
作者：
Bohgaki M;Matsumoto M;Atsumi T;Kondo T;Yasuda S;Horita T;Nakayama KI;Okumura F;Hatakeyama S;Koike T
抗磷脂综合征（APS）的特征是血栓形成和存在直接识别血浆β2-糖蛋白I（β2GPI）的抗磷脂抗体（aPL）。组织因子（TF）是外源性凝血系统的主要启动因子，在体外由aPL在单核细胞上诱导，部分解释了APS的病理生理学。我们以前报道过丝裂原活化蛋白激酶（MAPK）通路在aPL诱导的单核细胞TF表达中起重要作用。在这项研究中，我们确定血浆凝溶胶蛋白作为与β2GPI相关的蛋白质，通过使用免疫亲和层析和质谱分析。体内结合试验表明，内源性β2GPI与血浆凝溶胶蛋白相互作用，血浆凝溶胶蛋白通过纤连蛋白与整合素α 5 β1结合。在血浆凝溶胶蛋白存在下，β2GPI与细胞表面抗β2GPI单克隆抗体的结合增强。免疫印迹分析表明，抗β2GPI单克隆抗体可使p38 MAPK蛋白磷酸化，而抗整合素α 5 β1单克隆抗体可减弱p38 MAPK蛋白磷酸化。此外，抗β2GPI抗体处理可使纤连蛋白-整合素信号通路的下游分子粘着斑激酶磷酸化。这些结果表明，包括凝溶胶蛋白和整合素的分子参与了抗β2GPI抗体诱导的单核细胞MAPK通路，整合素是一个可能的治疗靶点，以改变APS患者的血栓前状态。
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.
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影响因子：
11.4
作者：
Bouma, B;de Groot, PG;Gros, P
通讯作者：
Gros, P
影响因子：
11.4
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Beyaert, R;Cuenda, A;Fiers, W
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Fiers, W
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作者：
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Kruithof, EKO
影响因子：
20.3
作者：
de Laat, B;Derksen, RHWM;de Groot, PG
通讯作者：
de Groot, PG
影响因子：
10.4
作者：
Espinola, RG;Liu, X;Pierangeli, SS
通讯作者：
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