MYELOPEROXIDASE-DEPENDENT GENERATION OF A TYROSINE PEROXIDE BY NEUTROPHILS

It has recently been shown that tyrosyl radicals react with superoxide to form a peroxide adduct of tyrosine. Since myeloperoxidase oxidizes tyrosine to its radical, and neutrophils and monocytes contain myelop eroxidase as well as produce superoxide, we have investigated whether tyrosine peroxide could be a significant product of tyrosine oxidation by these cells, Oxidation of tyrosine by purified myeloperoxidase and a superoxide generating system, and by stimulated human neutrophils, was found to generate peroxide adducts as detected in the xylenol oran ge (FOX) assay and by HPLC. Superoxide, hydrogen peroxide, and myelope roxidase were required for formation of the peroxide. Dityrosine was a lso formed in each system, and in the presence of superoxide dismutase , suppression of tyrosine peroxide formation gave elevated formation o f dityrosine, Quantitative estimates indicate that at physiological ty rosine concentration the peroxide is likely to be formed in preference to dityrosine and to be a significant product of neutrophils. This me tastable peroxide therefore has the potential to contribute to neutrop hil- or monocyte-mediated tissue injury. (C) 1997 Academic Press.