Cigarette Smoke-Mediated Oxidant Stress, Phagocytes, Vitamin C, Vitamin E, and Tissue Injury

Activated neutrophils, the predominant small circulating phagocytes, have the potential to generate enormous amounts of the reactive oxidants (ROS) hydrogen peroxide (H sub(2)O sub(2)) and hypochlorous acid (HOCl). The oxidant-generating enzyme is a membrane-associated, electron-transporting NADPH-oxidase that consists of a membrane-bound flavoprotein and a low-potential cytochrome, cytochrome b sub(245), as well as several cytosolic components. Activation of the dormant enzyme is achieved by several different transmembrane signalling systems involving phospholipase C, phospholipase A sub(2) and phospholipase D, acting individually or in concert depending on the nature of the stimulus of membrane-associated oxidative metabolism. It has been proposed that the point of convergence of the various second messengers generated by these diverse signalling systems is the calcium and phospholipid-dependent protein kinase, PKC.