Signal transduction during platelet-activating factor-induced lymphocyte binding to endothelial cells

Platelet-activating factor (PAF) is a lipid mediator of inflammation. PAF pretreatment of cultured endothelial cells leads to an increase in lymphocyte binding. We have analysed the intracellular signal transduction during this PAF-induced effect. The protein kinase C activator, phorbol 12-myristate, 13-acetate, mimicked PAF in the binding assay. Concomitantly, the protein kinase C (PKC) inhibitor H7 down-regulated the PAF-induced binding to nearly control level. Also dibutyryl-cAMP treatment of endothelial cells increased lymphocyte binding, but the protein kinase A inhibitor HA1004 did not alter the PAF-induced binding. Furthermore, PAF did not increase the level of cytosolic cAMP in the endothelial cells. Other second messengers, cGMP and Ca2+, had no effect on lymphocyte binding. These findings suggest that protein kinase C, but not other signal transduction pathway, is essential in the PAF-induced lymphocyte binding to endothelial cells.