ABSTRACT
Reactive oxygen species (ROS) are toxic products derived from oxygen metabolism and are involved in a number of human diseases, including inflammation, aging, carcinogenesis, degenerative diseases such as arthritis or Alzheimer’s disease, and all the conditions associated with ischemia/reperfusion injury (1-5). ROS, however, are also an important part of host defense mechanisms against infection. Following infection the host’s nonspecific phagocytic systems-neutrophils (in the case of an acute infection) and monocytes-macrophages (in the case of a more chronic infection)—ingest the invading microorganisms and kill them extracellularly or intracellularly by producing toxic mediators, among which are ROS. ROS production during phagocytosis occurs following activation of the respiratory burst enzyme NADPH oxidase, which transports electrons at the cell membrane and generates superoxide anions
( ) at the expense of NADPH. This complex enzyme can be activated via a number of different pathways, including ligand interactions with receptors associated with either phospholipase A2 or phospholipase C, and interactions with nonparticulate stimuli such as phorabol myristate acetate (PMA), a direct activator of protein
kinase C (6). Furthermore, in the presence of transition metals such as iron, and H2O2 can give rise to the extremely reactive hydroxyl radical via the Fenton reaction. During infection and phagocytosis, ROS are toxic to the microorganisms. The importance of ROS in anti-infectious defenses is exemplified by the diseases associated with a defect in NADPH oxidase, such as chronic granulomatous disease (CGD), which leads to overwhelming infections and death (7).
