ROLE OF MYELOPEROXIDASE IN THE RESPIRATORY BURST OF HUMAN-NEUTROPHILS

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 61  (3) , 483-492
Abstract
Myeloperoxidase (MPO), a heme enzyme present in the primary granules of polymorphonuclear leukocytes (PMN), was demonstrated to participate in the O2-dependent microbicidal activity of these cells. Evidence for the importance of MPO in this role comes in part from studies of normal PMN treated with the heme enzyme inhibitor, sodium azide. MPO apparently regulates the respiratory activity of PMN during phagocytosis. The role of MPO in PMN O2 metabolism was examined by studying parameters of the respiratory burst of PMN from a number of unrelated MPO-deficient subjects; in addition, the ability of heme enzyme inhibitors to duplicate the MPO-deficient state was studied by treating normal and MPO-deficient cells with these compounds. MPO-deficient PMN were found to have a time-dependent hypermetabolic response as assessed by measurement of O2 consumption, superoxide generation, H2O2 release and hexose monophosphate shunt activity. Catabolic pathways for H2O2 were normal, suggesting the increased recovery of O2 metabolites reflects increased production rather than decreased catabolism of H2O2. MPO may play an important role in terminating the respiratory burst of normal PMN. The 3 heme enzyme inhibitors studied were sodium azide, KCN and 3-aminotriazole, and they differed greatly in the degree to which they inhibited various enzymatic systems in the PMN. As a group, they exerted qualitatively similar effects on O2 metabolism of normal and of MPO-deficient PMN. Many of the mechanisms by which heme enzyme inhibitors influence PMN metabolism are independent of the inhibition of MPO. Conclusions from studies using such treatment of PMN should be interpreted with caution.