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

Luigi Biancone, Vincenzo Cantaluppi, Mariarosaria Boccellino, Benedetta Bussolati, Lorenzo Del Sorbo, Pier Giulio Conaldi, Adriana Albini, Antonio Toniolo, Giovanni Camussi

Research output: Contribution to journalArticle

Abstract

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 (WEB 2170, CV 3988, CV 6209, and BN 52021), suggesting that the synthesized PAF mediates the motogenic effect of Tat. This effect was also present on cells plated on a type-I collagen-, fibronectin-, or basement membrane extract- coated surface. Expression of PAF receptor-specific mRNA was detected in KS cells. In addition, examination of the cytoskeletal organization showed that Tat-mediated KS cell redistribution of actin filaments and shape change was also inhibited by a PAF receptor antagonist. Moreover, PAF receptor blockade prevented the up-regulation of β1 integrin and the down-regulation of αβ3 observed after stimulation of KS cells with 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 motility of KS cells.

Original languageEnglish
Pages (from-to)1731-1739
Number of pages9
JournalAmerican Journal of Pathology
Volume155
Issue number5
Publication statusPublished - Nov 1999

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Biancone, L., Cantaluppi, V., Boccellino, M., Bussolati, B., Del Sorbo, L., Conaldi, P. G., Albini, A., Toniolo, A., & Camussi, G. (1999). Motility induced by human immunodeficiency virus-1 Tat on Kaposi's sarcoma cells requires platelet-activating factor synthesis. American Journal of Pathology, 155(5), 1731-1739.