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[Superoxide-generating system in leukocytes: its activation mechanism and significance]
1Institute of Medical Science, University of Tokyo, Japan.
Abstract:
Leukocytes such as neutrophils, eosinophils, monocytes and B lymphocytes but not T lymphocytes nor NK cells have a special electron transport system on their plasma membrane and generate superoxide anion upon stimulation. Superoxide anion is released to the outside of the cells (or inside of phagosomes if they are phagocytes), where other active oxygen species are formed secondarily. These species may be used for killing infectious agents. Superoxide-generating system in these cells consists of a total of 5 proteins, i.e. 91- and 22-kDa subunits of cytochrome b558 in membrane and 21-, 47- and 65-kDa proteins in cytoplasm. Upon stimulation, a functionally active complex is formed in the membrane, which caries electrons from NADPH in the cytoplasm to molecular oxygen at the surface of the cells. Any defect in these components except the cytosolic 21-kDa protein (a small GTP binding protein, Rac) causes chronic granulomatous disease, an inherited disorder where leukocytes can not generate superoxide anion. The patients with this disease suffer from recurrent, life-threatening infections of catalase-positive microorganisms. This review will focus on active oxygen species formed during phagocytosis, components of superoxide-generating system in neutrophil and B lymphocytes, its activation mechanism and significance of active oxygen formation by the cells.