NITRIC-OXIDE SYNTHASE INHIBITORS ATTENUATE HUMAN MONOCYTE CHEMOTAXIS INVITRO

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.