Possible Involvement of Chemokine‐induced Platelet Activation in Thrombophilic Diathesis of Antiphospholipid Syndrome

Abstract

Among the heterogeneous antiphospholipid antibodies, many studies suggest that those directed to β2‐glycoprotein I (β2GPI) are the major pathogenic antibodies in antiphospholipid syndrome (APS). They have been shown to activate the coagulation pathway via several mechanisms, activate platelets via thrombin formation, and suppress fibrinolysis. Additionally, we propose another possible mechanism that involves certain chemokines and results in platelet activation. This hypothesis is based on the observations that anti‐β2GPI antibodies stimulated monocytes to secrete inflammatory cytokines such as IL‐1β and TNF‐α, which in turn stimulated vascular endothelial cells to express chemokines such as CX3CL1 and CCL5. CX3CL1 increased the ability of normal platelets to adhere to collagen at a high shear rate, while CCL5 induced platelet aggregation. Expression of tissue factor, IL‐1β, and TNF‐α by monocytes stimulated with anti‐β2GPI antibodies, as well as CX3CL1 and CCL5 by vascular endothelial cells stimulated with IL‐1β or TNF‐α were all suppressed by the NF‐κB–specific inhibitor DHMEQ. These results suggest that the NF‐κB pathway may be a potential therapeutic target relating to both the coagulation pathway and platelet activity.