Myeloperoxidase as an effective inhibitor of hydroxyl radical production. Implications for the oxidative reactions of neutrophils

Abstract

Hydroxyl radicals have been generated from hydrogen peroxide and superoxide (produced with xanthine oxidase), and an iron (EDTA) catalyst, and detected with deoxyribose, or in some cases with benzoate or α-keto-γ-methiolbutyric acid. Purified myeloperoxidase, and neutrophils stimulated with fMet-Leu-Phe and cytochalasin B, strongly inhibited this hydroxyl radical production in a concentration-dependent manner. Supernantants from stimulated cells also inhibited, and inhibition by cells or supernatant was prevented by azide. There was much less inhibition by myeloperoxidase-deficient neutrophils. Inhibition thus was due to myeloperoxidase released by the cells. With neutrophils stimulated with phorbol myristate acetate, which release very little myeloperoxidase, hydroxyl radical production was enhanced due to the additional superoxide produced by the cells. It is concluded that under conditions where neutrophils release myeloperoxidase as well as superoxide and hydrogen peroxide, breakdown of hydrogen peroxide by myeloperoxidase would make conditions unfavorable for hydroxyl radical production.