The synthesis of platelet-activating factor modulates chemotaxis of monocytes induced by HIV-1 Tat

HIV-1 Tat protein has been shown to induce chemotaxis and recruitment of mo nocytes. In the present study, we evaluated whether HIV-1 Tat protein was a ble to induce the synthesis of platelet-activating factor (PAF), which is a potent mediator of cell motility, and whether the synthesis of PAF was ins trumental in triggering Tat-induced monocyte chemotaxis. The results obtain ed indicate that Tat, but not gp120 and gp41, induced a time-dependent synt hesis of PAF from monocytes at concentration as low as 0.1 ng/ml. As inferr ed by the inhibitory effect of anti-fit-1 antibody and by the desensitizati on of monocytes following preincubation with vascular endothelial growth fa ctor, the synthesis of PAF by monocytes stimulated with Tat was induced by activation of vascular endothelial growth factor receptor 1. Moreover, the Tat-induced chemotaxis of monocytes was abrogated both by WEB 2170 and by C V 3988, two chemically unrelated PAF receptor antagonists, suggesting that the synthesized PAF modulates the chemotactic response of monocytes to Tat. In conclusion, the results of the present study indicate that Tat-induced PAF synthesis plays a critical role in triggering the events involved in th e migratory response of monocytes.