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

Lorenzo D. Del Sorbo, Antonella DeMartino, Luigi Biancone, Benedetta Bussolati, Pier Giulio Conaldi, Antonio Toniolo, Giovanni Camussi

Research output: Contribution to journalArticlepeer-review

Abstract

HIV-1 Tat protein has been shown to induce chemotaxis and recruitment of monocytes. In the present study, we evaluated whether HIV-1 Tat protein was able to induce the synthesis of platelet-activating factor (PAF), which is a potent mediator of cell motility, and whether the synthesis of PAF was instrumental in triggering Tat-induced monocyte chemotaxis. The results obtained indicate that Tat, but not gp120 and gp41, induced a time-dependent synthesis of PAF from monocytes at concentration as low as 0.1 ng/ml. As inferred by the inhibitory effect of anti-Flt-1 antibody and by the desensitization of monocytes following preincubation with vascular endothelial growth factor, 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 CV 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 the migratory response of monocytes.

Original languageEnglish
Pages (from-to)1513-1521
Number of pages9
JournalEuropean Journal of Immunology
Volume29
Issue number5
DOIs
Publication statusPublished - 1999

Keywords

  • Chemotaxis
  • HIV-1 Tat
  • Monocyte
  • Platelet-activating factor

ASJC Scopus subject areas

  • Immunology

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