ACTIVATED HUMAN NEUTROPHILS RAPIDLY BREAK DOWN NITRIC-OXIDE

Isolated human neutrophils produced no detectable (<10 nM) nitric oxid e (NO) before or after activation with phorbol 12-myristate 13-acetate (PMA) or a chemotactic peptide, N-formyl-L-methionyl-L-leucyl-L-pheny lalanine Physiological levels of NO (1 mu M) added before or after neu trophil activation had no effect on their respiratory burst oxygen con sumption, Neutrophils activated with PMA caused very rapid breakdown o f exogenously added NO, NO breakdown rates recorded at 250 nM NO mere 0.09 +/- 0.02 and 3.77 +/- 0.23 nmol NO/min/10(6) cells (n = 3) before and after activation respectively and addition of copper-zinc superox ide dismutase during activation significantly decreased this rate (1.0 6+/-0.09 nmol NO/min/10(6) cells (n=3)), suggesting that superoxide (0 (2)(-)) production was mainly responsible for the NO breakdown, These results suggest that activation of human neutrophils in vivo will dram atically decrease surrounding NO levels, potentially causing vasoconst riction, platelet aggregation and adhesion and peroxynitrite (ONOO-) f ormation. (C) 1997 Federation of European Biochemical Societies.