APS IgG诱导血液单核细胞TF表达及其干预药物探讨

Monocytes TF expression induced by APS IgG and inhibited by dilazep.

目的探讨抗磷脂综合征(APS)患者血清IgG体外诱导血液单核细胞表达组织因子(TF)的作用并探索某些药物对此作用的干预。方法刺激物作用于外周血单核细胞,经TF/Ⅶa产生因子X_a,判断单核细胞TF活性的表达;利用TF引物进行TagMan PCR,定量观察单核细胞TF mRNA表达。结果与健康人血清IgG比较,APS患者血清IgG显著增强单核细胞的TF表达;地拉卓呈量效递增性抑制APS IgG诱导单核细胞TF活性表达,腺苷受体拮抗剂—茶碱能中和地拉卓的这一抑制效应。结论 APS患者的自身抗体诱导血液单核细胞TF的表达,是患者血栓形成的主要机制之一;地拉卓通过腺苷受体途径干预APS IgG对单核细胞TF活性的诱导,可望成为治疗APS的新突破。

Objective To investigate whether the IgG from patients with antiphospholipid syndrome (APS) is capable of stimulating blood monocytes to express tissue factor (TF) and whether dilazep inhibits APS IgG-induced monocytes TF expression.Methods Freshly isolated peripheral blood monocytes were cultured in media containing different stimulants,the TF activity on monocytes was investigated by measuring factor VIIa-dependent generation of factor X a and the TF mRNA expression was investigated by real-time PCR (TaqMan PCR).Results APS IgG significantly increased monocytes TF expression,comparing with mormal IgG;dilazep inhibited APS IgG-induced monocytes TF activity in a dose-dependent fashion,theophylline,an adenoeine receptor antagonist,could counteract the inhibitory effect of dilazep on TF activity-Conclusions That autoantiphospholipid antibodies induce monocytes TF expression is contributed to the thrombotic diathesis in APS.Pharmacological agents that block monocytes TF activity,such as dilazep,are a novel therapeutic approach in APS.