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One of the subunits of the phagocyte NADPH oxidase is now recognized as a member of a family of NADPH oxidases, or NOX, present in cells other than phagocytes. Physiologic generation of ROS has been implicated in a variety of physiologic responses from transcriptional activation to cell proliferation and apoptosis. The increase in superoxide and hydrogen peroxide (H2O2) that results from stimulation of the NADPH oxidase is transient, in part due to the presence of the antioxidant enzymes, which return their concentrations to the prestimulation steady state level. Thus, the antioxidant enzymes may function in the \u201cturn-off\u201d phase of signal transduction by ROS. During its transient elevation, H2O2 may act as a modifier of key signaling enzymes through reversible oxidation of critical thiols. The rapid reaction of thiols with H2O2 when in their unprotonated state would provide a potential mechanism for the specificity that is necessary for physiologic cell signaling.<\/jats:p>","DOI":"10.1164\/rccm.2206007","type":"journal-article","created":{"date-parts":[[2004,12,11]],"date-time":"2004-12-11T17:37:44Z","timestamp":1102786664000},"page":"S4-S8","source":"Crossref","is-referenced-by-count":724,"title":["Reactive Oxygen Species and Cell Signaling: Respiratory Burst in Macrophage Signaling"],"prefix":"10.1093","volume":"166","author":[{"given":"Henry Jay","family":"Forman","sequence":"first","affiliation":[{"name":"Department of Environmental Health Sciences, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama; and Department of Pediatrics, Children's Hospital Los Angeles Research Institute, Keck School of Medicine, University of Southern California, Los Angeles, 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