Role of the Phagocyte in Host-Parasite Interactions XXVII. Myeloperoxidase-H(2)O(2)-Cl-Mediated Aldehyde Formation and Its Relationship to Antimicrobial Activity.

  • 1 April 1971
    • journal article
    • Vol. 3  (4) , 595-602
Abstract
Evidence is presented which suggests that the mechanism of action of the myeloperoxidase-H(2)O(2)-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 CO(2) were obtained. There was an absolute requirement for both H(2)O(2) and Cl(-) for decarboxylation by the myeloperoxidase-containing granules. The myeloperoxidase-H(2)O(2)-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-H(2)O(2)-Cl(-) system but had no effect on the myeloperoxidase-H(2)O(2)-I(-) bactericidal system. Since the myeloperoxidase-H(2)O(2)-I(-) system does not participate in amino acid decarboxylation, its mechanism of antimicrobial action appears to be different from that found with Cl(-).