ACTIVATION OF CULTURED VASCULAR ENDOTHELIAL-CELLS BY ANTIPHOSPHOLIPID ANTIBODIES

Circulating antiphospholipid antibodies (aPL) are associated with a syndrome of thrombosis, recurrent fetal loss, and thrombocytopenia, We have demonstrated the activation of cultured human umbilical vein endothelial cells (HUVEC) by IgG from patients with anticardiolipin antibodies (aCL). Incubation of HUVEC for 4 h with purified IgG (100 mu g/ml) from patients with high-titer aCL induced a 2.3-fold increase in monocyte adhesion over that seen in HUVEC incubated with IgG's from normal subjects, The effect of aCL was not attributable to LPS contamination, Fc receptors, or immune complexes; Monocyte adhesion was not induced when the aCL were added in serum-free media but was restored by the addition of purified beta(2)GP1, previously described as a necessary cofactor for aCL reactivity. Purified rabbit polyclonal IgG raised against beta(2)GP1 also induced monocyte adhesion when incubated with HUVEC. Preadsorption of patient serum with cardiolipin reduced monocyte adhesion by 60%. Immunofluorescent microscopy demonstrated that endothelial tells incubated with patient IgG expressed cell adhesion molecules, including E-selectin, vascular cell adhesion molecule-1, and intracellular adhesion molecule-1, These data support the hypothesis that aPL activate vascular endothelial cells, thereby leading to a prothrombotic state.