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Role of the Phagocyte in Host-Parasite Interactions XXVII. Myeloperoxidase-H₂O₂-Cl^–-Mediated Aldehyde Formation and Its Relationship to Antimicrobial Activity

¹ Department of Pathology and Medical Research, St. Margaret's Hospital, and Department of Obstetrics and Gynecology, Tufts University School of Medicine, Boston, Massachusetts 02125

ABSTRACT

Evidence is presented which suggests that the mechanism of action of the myeloperoxidase-H₂O₂-Cl^– antimicrobial system in the phagocyte is by the formation of aldehydes. Aldehyde production resulting from myeloperoxidase-mediated decarboxylation and deamination of alanine was quantitated with 20,000-g granules from guinea pig polymorphonuclear leukocytes serving as the enzyme. Equimolar quantities of acetaldehyde and CO₂ were obtained. There was an absolute requirement for both H₂O₂ and Cl^– for decarboxylation by the myeloperoxidase-containing granules. The myeloperoxidase-H₂O₂-Cl^– system decarboxylated both D- or L-alanine equally and had a pH optimum of 5.3. Decarboxylation of L-alanine by intact guinea pig polymorphonuclear leukocytes was increased 2.5-fold by phagocytosis. Guaiacol peroxidation by the granules was inhibited 90% in the presence of Cl^– at acid pH. Under these conditions, decarboxylation and deamination of amino acids by myeloperoxidase were significantly stimulated, resulting in aldehyde production. Taurine, a competitive inhibitor of amino acid decarboxylation, inhibited bactericidal activity of the myeloperoxidase-H₂O₂-Cl^– system but had no effect on the myeloperoxidase-H₂O₂-I^– bactericidal system. Since the myeloperoxidase-H₂O₂-I^– system does not participate in amino acid decarboxylation, its mechanism of antimicrobial action appears to be different from that found with Cl^–.

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