title: Nitric oxide synthase inhibitors attenuate human monocyte chemotaxis in vitro.
abstract: Nitric oxide synthase (NOS) inhibitors have been shown to modulate neutrophil migration. We hypothesized that the NOS inhibitors NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine methyl ester (L-NAME), and L-canavanine (L-CAN) also modulate human peripheral blood monocyte chemotaxis. To test this hypothesis, monocyte chemotaxis toward formylmethionylleucyl-phenylalanine (fMLP) was assessed using a modified blindwell chemotaxis chamber technique. L-NMMA and L-NAME, but not D-NMMA or L-CAN, significantly attenuated fMLP-induced monocyte chemotaxis (P < .05). L-Arginine and sodium nitroprusside, but not D-arginine, reversed NOS inhibitor-induced responses. Dibutryl cyclic guanyl monophosphate (cGMP) attenuated the inhibitory effects of L-NMMA on monocyte chemotaxis (P < .05). Finally, fMLP increased cGMP generation by monocytes, which was significantly attenuated by L-NMMA (P < .05). These data indicate that the L-arginine/NO biosynthetic pathway regulates human monocyte chemotaxis in vitro.
authors.affiliation: Research Service, Department of Veterans Affairs Medical Center, Omaha, Nebraska.
authors.forename: S N
authors.initials: SN
authors.lastname: Belenky
authors.forename: R A
authors.initials: RA
authors.lastname: Robbins
authors.forename: I
authors.initials: I
authors.lastname: Rubinstein
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002172:Canavanine / Q000494:pharmacology*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D006801:Humans; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology; D019323:omega-N-Methylarginine
chemical_list: D009599:Nitroprusside; D019323:omega-N-Methylarginine; D003995:Dibutyryl Cyclic GMP; D002172:Canavanine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester