Motility induced by human immunodeficiency virus-1 Tat on Kaposi's sarcomacells requires platelet-activating factor synthesis

In the present study, we evaluated whether motility of Kaposi's sarcoma (KS ) spindle cells induced by HIV-1 Tat protein is dependent on the synthesis of platelet-activating factor (PAF). The results obtained indicate that Tat induced a dose-dependent synthesis of PAF from KS cells at a concentration as low as 0.1 ng/ml. PAF production started rapidly after Tat stimulation, peaking at 30 minutes and declining thereafter. Tat-induced cell migration was also a rapid event starting at 30 minutes. The motility was abrogated by addition of a panel of chemically unrelated PAF receptor antagonists (WE B 2170, CV 3988, CV 6209, and BN 52021), suggesting that the synthesized PA F mediates the motogenic effect of Tat. This effect was also present on cel ls plated on a type-I collagen-, fibronectin-, or basement membrane extract -coated surface. Expression of PAF receptor-specific mRNA was detected in K S cells. In addition, examination of the cytoskeletal organization showed t hat Tat-mediated KS cell redistribution of actin filaments and shape change was also inhibited by a PAF receptor antagonist. Moreover, PAF receptor bl ockade prevented the up-regulation of pi integrin and the down-regulation o f alpha v beta 3 observed after stimulation of KS cells with Tat In conclus ion, the results of the present study indicate that Tat-induced PAF synthes is plays a critical role in triggering the events involved in motility of K S cells.