Background:
Nitric Oxide (NO) is a key signalling molecule that has an important role in
inflammation. It can be secreted by endothelial cells, neutrophils, and other cells, and once in circulation,
NO plays important roles in regulating various neutrophil cellular activities and fate.
Objective:
To describe neutrophil cellular responses influenced by NO and its concomitant compound
peroxynitrite and signalling mechanisms for neutrophil apoptosis.
Methods:
Literature was reviewed to assess the effects of NO on neutrophils.
Results:
NO plays an important role in various neutrophil cellular activities and interaction with other
cells. The characteristic cellular activities of neutrophils are adhesion and phagocytosis. NO plays a protective
role in neutrophil-endothelial interaction by preventing neutrophil adhesion and endothelial cell
damage by activated neutrophils. NO suppresses neutrophil phagocytic activity but stimulates longdistance
contact interactions through tubulovesicular extensions or cytonemes. Neutrophils are the main
source of superoxide, but NO flow results in the formation of peroxynitrite, a compound with high biological
activity. Peroxynitrite is involved in the regulation of eicosanoid biosynthesis and inhibits endothelial
prostacyclin synthase. NO and peroxynitrite modulate cellular 5-lipoxygenase activity and leukotriene
synthesis. Long-term exposure of neutrophils to NO results in the activation of cell death mechanisms
and neutrophil apoptosis.
Conclusion:
Nitric oxide and the NO/superoxide interplay fine-tune mechanisms regulating life and
death in neutrophils.
Isolation and molecular cloning of prostacyclin synthase from bovine endothelial cells.
