Histamine reduces GPIb?-mediated adhesion of platelets to TNF-?-activatedvascular endothelium

Histamine and tumor necrosis factor-? (TNF-?) are critical mediators of acute and chronic inflammation that are generated by mast cells and macrophages in atherosclerotic lesions or systemically during allergic attacks. Both of them induce activation of vascular endothelium and thus may play a role in thrombosis. Here we studied the interplay between histamine and TNF-? in glycoprotein (GP) Ib?-mediated platelet adhesion to cultured human vascular endothelial cells under static and shear flow conditions. The stimulation of endothelial cells with histamine or TNF-? increased the number of adherent or slow rolling GP Ib?-coated microbeads or washed human platelets. However, the application of histamine to endothelium pre-activated by TNF-? inhibited GP Ib?-mediated platelet adhesion. These effects were found to be associated with changes in the concentration of ultra large von Willebrand factor (ULVWF) strings anchored to endothelium. The results of this study indicate that histamine released during mast cell degranulation may cause or inhibit thrombosis, depending on whether it acts on resting endothelial cells or on cells pre-activated by other inflammatory stimuli.