Glutathione and Glutathione Transferase Omega 1 as Key Posttranslational Regulators in Macrophages

The cytoplasm of an activated macrophage is a dangerous place due to the accumulation of reactive oxygen species (ROS), which can perturb cytoplasmic oxidative balance. Macrophage activation through monocyte recruitment in tissues occurs in a highly regulated manner upon detection of microbial pathogen-associated molecular patterns (PAMPs), such as the Gram-negative bacterial cell wall component lipopolysaccharide (LPS), stimulating ROS production. ROS can be generated from many cellular processes, either directly or as a result of incomplete reduction of free radicals (1). One of the main sources of ROS is the NADPH oxidase (NOX), a specialized transmembrane protein complex that generates superoxide (O2–), which has been implicated in several inflammatory diseases (2). The generation of ROS can also stem from the mitochondrial electron transport chain, due to insufficient reduction of superoxide anions. Another source is the inducible form of nitric oxide synthase 2 (iNOS). iNOS produces nitric oxide from L-arginine and is known to play key roles in macrophage function (3,4).