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 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.
Del Sorbo
L
L
Dipartimento di Medicina Interna, Università di Torino, Italy.
DeMartino
A
A
Biancone
L
L
Bussolati
B
B
Conaldi
P G
PG
Toniolo
A
A
Camussi
G
G
D001381:Azepines / Q000494:pharmacology; D002633:Chemotaxis / Q000502:physiology*; D015696:Gene Products, tat / Q000378:metabolism* / Q000494:pharmacology; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus
D001381:Azepines; D015696:Gene Products, tat; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; D054322:tat Gene Products, Human Immunodeficiency Virus; C037913:CV 3988; C063964:bepafant