目的:探讨抗β2糖蛋白Ⅰ(抗β2GPⅠ)抗体诱导血液单核细胞表达组织因子(TF)活性的机制。方法:利用纯化的抗磷脂综合征(APS)患者血清IgG、单克隆抗β2GPⅠ抗体、抗Annexin A2抗体等刺激血液单核细胞及单核细胞株,通过凝血因子Xa的生成量,判断细胞TF活性的表达;利用Western杂交技术检测单核细胞膜表面Annexin A2的表达;采用免疫细胞化学染色判断单核细胞膜表面Annexin A2、β2GPⅠ、抗β2GPⅠ抗体的结合情况。结果:APS患者血清IgG和抗β2GPⅠ抗体显著增强单核细胞TF的表达;单核细胞膜表达的Annexin A2与β2GPⅠ/抗β2GPⅠ结合成复合物,引发细胞TF表达增强;抗Annexin A2抗体可抑制复合物的这种作用。结论:细胞表面Annexin A2介导β2GPⅠ/抗β2GPⅠ诱导单核细胞表达TF活性,是APS血栓形成的机理之一。
Objective: To explore the mechanisms of anti-β2Ⅰ -induced tissue factor activity on monocytes. Methods: The monocytes were cultured in media containing purified APS IgG or anti-β2Ⅰ or anti-Annexin A2 and other agonists and the TF activity on monocytes was investigated by measuring generation of factor X a. The expression of Annexin A2 on the monocytes membrane was observed by Western Blotting and the binding situation of Annexin A2 withβ2GPⅠ/anti-β2Ⅰ on the monocytes mambrane was investigated by cellular immunochemistry staining. Results: APS IgG as well as anti-β2Ⅰ antibody significantly increased monocytes tissue factor activity. Monocytes expressed the Annexin A2 which could bind to exogenous β2GPⅠ/anti-β2Ⅰ and induce TF activity. Anti-Annexin A2 antibody could inhibit the effects of these compound. Conclusion: Annexin A2 mediatesβ2Ⅰ/anti-β2Ⅰ compound-induced tissue factor activity on monocytes, which is contributed to the thrombotic diathesis in APS.