Platelet-activating factor synthesis by neutrophils, monocytes, and endothelial cells is modulated by nitric oxide production.
Nitric oxide (NO) and platelet-activating factor (PAF) can modulate the interaction between endothelial lining and circulating leukocytes. Several studies implicated the production of PAF and NO in the pathogenesis of microcirculatory alterations occurring in septic shock. However, the reciprocal interaction between PAF and NO has not been fully elucidated. In the present study, we evaluated whether the basal synthesis of NO could modulate the production of PAF by neutrophils (PMN), monocytes (MO), and endothelial cells (EC) unstimulated or stimulated with lipopolysaccharides (LPS) or tumor necrosis factor (TNF). PMN, MO, and EC, when incubated with N(omega)-nitro-L-arginine methyl ester (L-NAME) spontaneously synthesized PAF, with an early peak at 30 min. The effective inhibition of NO production was visualized on MO cells as generation of fluorescence reactivity by cell-permeable NO reactive dye DAF-2 DA. Also, monomethyl-L-arginine (L-NMMA) induced PAF synthesis by PMN, whereas the biologically inactive D-enantiomers of NAME (D-NAME) and of NMMA (D-NMMA) did not. Stimulation of PMN with L-NAME in presence of the exogenous NO donor nitroprusside, of the NO secondary mediator cGMP, or of the NO synthase substrate L-arginine reduced PAF synthesis, suggesting the involvement of an NO-dependent pathway on the modulation of PAF synthesis. The synthesis of PAF was enhanced by combined treatment with L-NAME and TNF or LPS. These results indicate an inhibitor effect of NO on the spontaneous and TNF or LPS-induced synthesis of PAF by human PMN, MO, and EC.
Mariano
Filippo
F
Department of Area of Medicine, Nephrology and Dialysis Unit, CTO Hospital, Turin, Italy.
Bussolati
Benedetta
B
Migliori
Massimiliano
M
Russo
Simona
S
Triolo
Giorgio
G
Camussi
Giovanni
G
D000328:Adult; D001120:Arginine / Q000494:pharmacology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000494:pharmacology; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000096:biosynthesis* / Q000235:genetics; D013237:Stereoisomerism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester