Motility induced by human immunodeficiency virus-1 Tat on Kaposi's sarcoma cells 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 (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 beta1 integrin and the down-regulation of alphavbeta3 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.
Biancone
L
L
Cattedra di Nefrologia, Dipartimento di Medicina Interna, Università di Torino, Torino, Italy.
Cantaluppi
V
V
Boccellino
M
M
Bussolati
B
B
Del Sorbo
L
L
Conaldi
P G
PG
Albini
A
A
Toniolo
A
A
Camussi
G
G
D001381:Azepines / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000494:pharmacology; D015696:Gene Products, tat / Q000378:metabolism* / Q000494:pharmacology; D046934:Ginkgolides; D015497:HIV-1; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011726:Pyridinium Compounds / Q000494:pharmacology; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012514:Sarcoma, Kaposi / Q000378:metabolism / Q000473:pathology*; D014230:Triazoles / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D054322:tat Gene Products, Human Immunodeficiency Virus
D001381:Azepines; D004224:Diterpenes; D005343:Fibrinolytic Agents; D015696:Gene Products, tat; D046934:Ginkgolides; D007783:Lactones; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011726:Pyridinium Compounds; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; D054322:tat Gene Products, Human Immunodeficiency Virus; C053321:CV 6209; C037913:CV 3988; C063964:bepafant; C045856:ginkgolide B