Myeloperoxidase

Phagocytes respond to stimulation with a burst of oxygen consumption, and m uch, if not all, of the extra oxygen consumed in the respiratory burst is c onverted first to the superoxide anion and then to hydrogen peroxide (H2O2) . Myeloperoxidase (MPO), which is released from cytoplasmic granules of neu trophils and monocytes by a degranulation process, reacts with the H2O2 for med by the respiratory burst to form a complex that can oxidize a large var iety of substances. Among the latter is chloride, which is oxidized initial ly to hypochlorous acid, with the subsequent formation of chlorine and chlo ramines. These products of the MPO-H2O2-chloride system are powerful oxidan ts that can have profound biological effects. The primary function of neutr ophils is the phagocytosis and destruction of microorganisms, and the relea se of MPO and H2O2 into the phagosome containing the ingested microorganism generally leads to a rapid microbicidal effect. Neutrophils from patients with chronic granulomatous disease (CGD) have a microbicidal defect that is associated with the absence of a respiratory burst and, thus, H2O2 product ion. Neutrophils from patients with a hereditary MPO deficiency, who lack M PO, also have a microbicidal defect, although it is not as severe as that s een in CGD. MPO and H2O2 also can be released to the outside of the cell wh ere a reaction with chloride can induce damage to adjacent tissue and, thus , contribute to the pathogenesis of disease. It has been suggested that pul monary injury, renal glomerular damage, and the initiation of atherosclerot ic lesions may be caused by the MPO system.