Key result
Human neutrophil activation accelerates nitric oxide breakdown ~42-fold, likely driven by superoxide production.
Why the study?
The effect of activated human neutrophils on surrounding nitric oxide levels and the mechanisms of NO breakdown were not well characterized.
Absolute Event Rate: 3.77% vs 0.09%
Activated human neutrophils rapidly break down nitric oxide, likely via superoxide production, which may decrease surrounding NO levels in vivo and potentially cause vasoconstriction and platelet aggregation.
Isolated human neutrophils produced no detectable (< 10 nM) nitric oxide (NO) before or after activation with phorbol 12-myristate 13-acetate (PMA) or a chemotactic peptide, N-formyl-L-methionyl-L-leucyl-L-phenylalanine. Physiological levels of NO (1 microM) added before or after neutrophil activation had no effect on their respiratory burst oxygen consumption. Neutrophils activated with PMA caused very rapid breakdown of exogenously added NO. NO breakdown rates recorded at 250 nM NO were 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 superoxide dismutase during activation significantly decreased this rate (1.06 +/- 0.09 nmol NO/min/10(6) cells (n = 3)), suggesting that superoxide (O2-) production was mainly responsible for the NO breakdown. These results suggest that activation of human neutrophils in vivo will dramatically decrease surrounding NO levels, potentially causing vasoconstriction, platelet aggregation and adhesion and peroxynitrite (ONOO-) formation.
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McBride et al. (1997) studied this question. Activation with PMA or chemotactic peptide vs. Before activation was evaluated on Nitric oxide breakdown rate (nmol NO/min/10^6 cells). Activation of isolated human neutrophils caused a rapid breakdown of exogenously added nitric oxide (from 0.09 to 3.77 nmol NO/min/10^6 cells), likely driven by superoxide production.
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