白血球膜における活性酸素の産生

抄録

Primary function of neutrophils is phagocytosis and killing of pathogenic microorganisms, and oxygen metabolites are known as principal microbicidal factor in neutrophils. However, oxygen metabolites are often toxic to living body, since they are too reactive to cause inflammation, cancer, aging, etc. It has been indicated that NADPH oxidase associated with plasma membranes is responsible for the production of superoxide anion (O-2), which is followed by the production of other toxic active oxygens such as hydrogen peroxide, hydroxyl radical and singlet oxygen. On phagocytosis or by exposure to certain stimuli, NADPH oxidase is activated from the dormant state. But, the biochemical mechanism for the activation of NADPH oxidase has not been fully clarified, recent intensive studies using cell-free activation systems and neutrophils from patients with chronic granulomatous disease (CGD), in which O-2production is genetically deficient, showed that NADPH oxidase on the plasma membrane consists of many components existing not only in the plasma membrane but also in the cytosol. We found that phosphorylation of 48K protein (s) was increased in human neutrophils in parallel with the activation of NADPH oxidase after the treatment with PMA, a protein kinase C activator, and that the 48K protein phosphorylation was deficient or abnormal in many types of CGD neutrophils. In this paper, we review the activation mechanism with special references to the assembly of the components of NADPH oxidase on the plasma membranes.