Redox Signaling in Macrophages

Macrophages are phagocytic cells that produce and release reactive oxygen species (ROS) in response to phagocytosis or stimulation with various agents. The enzyme responsible for the production of superoxide and hydrogen peroxide is a multi-component NADPH oxidase that requires assembly at the plasma membrane to function as an oxidase. In addition to participating in bacterial killing, ROS, which have recently been shown to be produced enzymatically by non-phagocytic cells, have been implicated in inflammation and tissue injury. These toxic effects have been largely explored over the years and these studies have overshadowed initial observations supporting a role for ROS in modulating cellular function. In recent years, it has become increasingly evident that ROS can function as second messengers and, at low levels, can activate signaling pathways resulting in a broad array of physiological responses from cell proliferation to gene expression and apoptosis. Macrophages can also produce large amounts of nitric oxide (nitrogen monoxide, *NO). *NO was first identified as the endothelial-derived relaxing factor, EDRF and its role in the signaling pathway leading to its physiological effect was rapidly established. The ability of *NO to react with O(2)(*-) to produce peroxynitrite (ONOO(-)) was later recognized. As it is diffusion-limited, this reaction is more likely to occur in cells like macrophages that produce both ROS and RNS. In this review, we will summarize the current knowledge in redox signaling, and describe more specifically studies that are particular to macrophages.