Biomarkers of myeloperoxidase-derived hypochlorous acid

Hypochlorous acid is the major strong oxidant generated by neutrophils. The heme enzyme myeloperoxidase catalyzes the production of hypochlorous acid from hydrogen peroxide and chloride. Although myeloperoxidase has been impl icated in the tissue damage that occurs in numerous diseases that involve i nflammatory cells, it has proven difficult to categorically demonstrate tha t it plays a crucial role in any pathology. This situation should soon be r ectified with the advent of sensitive biomarkers for hypochlorous acid. In this review, we outline the advantages and limitations of chlorinated tyros ines, chlorohydrins, 5-chlorocytosine, protein carbonyls, antibodies that r ecognize HOCl-treated proteins, and glutathione sulfonamide as potential bi omarkers of hypochlorous acid. Levels of 3-chlorotyrosine and 3,5-dichlorot yrosine are increased in proteins after exposure to low concentrations of h ypochlorous acid and we conclude that their analysis by gas chromatography and mass spectrometry is currently the best method available for probing th e involvement of oxidation by myeloperoxidase in the pathology of particula r diseases. The appropriate use of other biomarkers should provide compleme ntary information. (C) 2000 Elsevier Science Inc.