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

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RESUMO

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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