EFFECT OF VARIOUS AGONISTS ON NITRIC-OXIDE GENERATION BY HUMAN POLYMORPHONUCLEAR LEUKOCYTES

Nitric oxide,generation is involved in a range of diseases involving p olymorphonuclear leukocytes. The aim of this study was to determine wh ether human polymorphonuclear leukocytes are able to generate nitric o xide and to investigate the time course of its generation after stimul ation with 10(-7) M N-formyl-methionyl-leucyl-phenylalanine, 60 ng/ml phorbol myristate acetate, 10(-7) M? concanavalin A, and 10(-7) M plat elet activating factor. Stimulation of human polymorphonuclear leukocy tes with N-formyl-methionyl-leucyl-phenylalanine and phorbol myristate acetate caused sustained nitric oxide generation, reaching maximal va lues of 1,105+/-361 nM (n=32) and 628+/-119 nM (n=30), respectively. P latelet activating factor did not affect nitric oxide production (maxi mal value 29+/-7 nM, n=8), whereas concanavalin A caused only a slight increase (102+/-24 nM, n=8) when compared with resting cells control (26+/-6 nM, n=8). Human polymorphonuclear leukocytes were able to resp ond to both consecutive and alternate N-formyl-methionyl-leucyl-phenyl alanine and phorbol myristate acetate stimulation with nitric oxide ge neration. Nitric oxide generation was inhibited by specific inhibitors (N-omega-nitro-L-arginine and N(omega-)monomethyl-L-arginine) and res tored with L-arginine. We provide, to our knowledge, the first direct evidence that human neutrophils generate nitric oxide.