Nitric oxide synthase inhibitors attenuate human monocyte chemotaxis in vitro

Nitric oxide synthase (NOS) inhibitors have been shown to modulate neutrophil migration. We hypothesized that the NOS inhibitors N G ‐monomethyl‐L‐ arginine (L‐NMMA), N G ‐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 formylmethionyl‐ leucyl‐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.