Nitric Oxide in Life and Death of Neutrophils

Abstract

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.