Activation of monocytes and granulocytes by stimulating antiphospholipid antibodies

Abstract

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by arterial/venous thrombosis or pregnancy complications caused by the appearance of antiphospholipid antibodies (aPLs). The presence of aPLs apparently constitutes a risk factor for arterial and/or venous thrombotic complications. However, the precise mechanisms underlying thrombotic complications in these patients have not yet been elucidated. In this study, we investigated the effects of IgG-aPLs on monocytes and granulocytes associated with thrombus formation and vascular inflammation by evaluating cell surface and cell adhesion. As a result, we found that the percentage of activated monocytes (CD14+/CD16+) was significantly increased by IgG-aPL stimulation compared with no stimulation. In addition, we confirmed the granulocyte surface CD44 expression after IgG-aPL stimulation. There was no significant change in the percentage of CD44-positive cells, but the percentages of granulocytes expressing CD44 v6 and overexpressing CD44 were increased by IgG-aPL stimulation. Moreover, IgG-aPL stimulation enhanced the adhesion of granulocytes to the extracellular matrix (fibronectin, collagen I, and collagen IV). We found that the presence of IgG-aPLs increases the percentage of activated monocytes associated with inflammatory and autoimmune diseases. CD14+/CD16+ monocytes may be involved in the pathogenesis of APS. We also found that IgG-aPLs may promote the inflammatory responses of granulocytes and their adhesion to vascular endothelial cells. These findings suggest that aPLs may induce the inflammatory responses of vascular endothelial cells and provide a scaffold for thrombus formation. Furthermore, granulocytes may have a “prothrombotic tendency” toward thrombus through their increased adhesive ability to vascular endothelial cells in vivo, in addition to the inflammatory state induced by IgG-aPL stimulation.