Signaling by the respiratory burst in macrophages

During phagocytosis or stimulation with a wide variety of agents, macrophag es and other phagocytic cells produce reactive oxygen species (ROS) through activation of a multicomponent NADPH oxidase. ROS production through relat ed NADPH oxidases has recently been demonstrated in several other cell type s. Furthermore, the physiological generation of ROS production has now been clearly implicated in activating signaling pathways resulting in a broad a rray of physiological responses from cell proliferation to gene expression and apoptosis. This brief review suggests that: 1) hydrogen peroxide and su peroxide, but not the hydroxyl radical, function as second messengers; 2) a ntioxidant enzymes function in the "turn-off" phase of signal transduction; 3) the chemistry of thiols is critical in redox signaling; and 4) the prim ary physiological role of the respiratory burst in macrophages may be in re dox signaling rather than microbicidal activity.