Reactive Oxygen Species Generation in Neutrophils: Modulation by Nitric Oxide

Abstract

Neutrophils, the phagocytic and short-lived cells, were initially noticed for powerful microbicidal action; however, their specific depletion helped in gaging their unidentified importance in myocardial ischemia-reperfusion injury. Moreover, change in the number of circulating/or migrating neutrophils at the inflammatory site attracted scientists to investigate their significance in various pathologies. Importantly, inhibition of neutrophil recruitment and reactive oxygen species (ROS) generation ability improved cardiac function including cardiac hypertrophy and remodeling in diverse conditions. ROS and protease release from neutrophils have been associated with tissue damages including myocarditis, myocardial infarction, and ischemia-reperfusion injury. Nitric oxide (NO), a pleotropic molecule, modulates various physiological functions including vascular tone and cardiac homeostasis. NO controls most of neutrophil functions including ROS generation that influence release of several inflammatory mediators. Neutrophil ROS that depends on NADPH oxidase (NOX-2) system is regulated by diverse mechanisms including posttranslational modifications, protein interactions, and cofactors. In this chapter, we discuss various regulatory mechanisms involved in NO-mediated modulation of neutrophil reactive oxygen and nitrogen species (RONS) generation, and also NO production by neutrophils, which has impacted our understanding of the inflammatory diseases including cardiovascular disorders.