Polymorphonuclear (PMN) cells prevent infection by ingesting and killing microorganisms, but proteases, oxidants, and other toxins released by PMN cells damage host tissue. Our aim was to determine the factors that regulate oxidant production by myeloperoxidase (MPO) following secretion of MPO into the medium. Polymorphonuclear cells stimulated with phorbol myristate acetate (PMA) or opsonized zymosan particles released superoxide free radicals (;The steps leading to MPO inactivation were studied further in a cell-free model system containing purified MPO, chloride, phosphate buffer, pH 7.0, and xanthine oxidase with acetaldehyde as a source of peroxide. In the model system, MPO was not inactivated, but accumulated in Compound III. Cupric (+2) or cuprous (+1) ions at concentrations as low as 0.1 ;Compound III was prepared, incubated with a source of superoxide and cupric ions, and the rate of inactivation was measured and compared with the rate of inactivation of ferric MPO. From these results, a mechanism for MPO inactivation is proposed... |