Showing papers on "Myeloperoxidase published in 1970"

Myeloperoxidase: Contribution to the Microbicidal Activity of Intact Leukocytes

Abstract: Azide and, to a lesser extent, cyanide inhibit the microbicidal activity of myeloperoxidase and of intact normal leukocytes, but they have little or no effect on peroxidase-negative leukocytes. The contribution of the azide-sensitive (peroxidase-dependent?) systems to the total microbicidal activity of normal leukocytes is considerable. The azide-insensitive antimicrobial systems are more highly developed in peroxidase-negative leukocytes than in normal leukocytes, thus suggesting an adaptation.

Peroxidase-mediated virucidal systems.

Abstract: Peroxidase (myeloperoxidase or lactoperoxidase), hydrogen peroxide, and a halide such as iodide, bromide, or chloride form a potent virucidal system that is effective against polio and vaccinia viruis, particularly at a low pH. The peroxidase-halide-hydrogen peroxide system may contribute to the host defense against certain viral infections.

Function of h(2)o(2), myeloperoxidase, and hexose monophosphate shunt enzymes in phagocytizing cells from different species.

Abstract: The effect of phagocytosis on the H2O2 production and myeloperoxidase (MPO) activities of leukocytes from various species was investigated. The intracellular distribution of MPO, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase (6PGDH) of resting and phagocytizing guinea pig polymorphonuclear leukocytes has also been studied. Phagocytizing cells produce more H2O2 than the corresponding resting cells. This has been found to be true for human peripheral polymorphonuclear leukocytes, mouse peritoneal macrophage, and guinea pig and rat peritoneal polymorphonuclear leukocytes. All of these cells, except rabbit alveolar macrophages, have significant MPO activity. Generally an increased activity is noted with phagocytizing cells. Homogenization and differential centrifugation of guinea pig peritoneal polymorphonuclear leukocytes indicate that the whole homogenate and its fractions from phagocytizing cells have significantly higher MPO and NADPH oxidase activities, when compared to the corresponding fractions from the resting cells. The 27,000 × g supernatant fluid from phagocytizing cells has 6-fold more MPO and 2.5-fold more NADPH oxidase activity than similar supernatant fractions from resting cells. The enzyme 6PGDH was unaffected by phagocytosis. The relationship of these stimulated activities to the intracellular bactericidal function of the phagocytes has been discussed.

Interaction of Aspergillus fumigatus Spores with Human Leukocytes and Serum.

Abstract: Serum was necessary for optimal phagocytosis of Aspergillus fumigatus spores by human leukocytes, and its opsonic capacity was greatly diminished by heat inactivation (56 C, 30 min). A germination assay, described in this report, was developed to study the fate of phagocytized spores. After incubation for 3 hr with normal leukocytes and serum, spores ingested by peripheral blood neutrophils and monocytes remained viable. Since we had previously found that myeloperoxidase (MPO), a lysosomal enzyme of human neutrophils and monocytes, exerted fungicidal activity against Candida albicans when combined with H(2)O(2) and chloride or iodide, the effects of these substances on A. fumigatus spores were examined. Spore viability was not impaired by MPO alone, H(2)O(2) alone, or KI alone, but high concentrations of KI and H(2)O(2) in combination caused marked inhibition of subsequent germination. MPO imparted fungicidal activity to concentrations of KI and H(2)O(2) that lacked any effect in its absence. NaCl, in combination with MPO and H(2)O(2), was far less effective than the iodide salt against A. fumigatus. The relative ineffectiveness of chloride in this system could underly the apparent inability of human neutrophils to kill ingested A. fumigatus spores, despite their competence to kill C. albicans.

Role of the Phagocyte in Host-Parasite Interactions XXIV. Aldehyde Generation by the Myeloperoxidase-H(2)O(2)-Chloride Antimicrobial System: a Possible In Vivo Mechanism of Action.

Abstract: Myeloperoxidase (MPO), H2O2, and chloride ions in the presence of bacteria form aldehydes and are bactericidal. The use of heat-inactivated MPO prevented both killing and aldehyde generation. Decarboxylation and deamination of carboxyl and amino group substrates arising from the bacterial surface may participate in the reaction which yields aldehydes. Bacterial contact was essential for killing. Decarboxylation and bactericidal activities were noted when physiological concentrations of chloride were used. When MPO was replaced with horseradish peroxidase (HPO) in the chloride medium, decarboxylation and bactericidal activities were no longer noted. In contrast, iodide functioned in the antimicrobial system with either MPO or HPO. The iodide concentrations required were at least sixfold greater than circulating blood iodide levels. Moreover, decarboxylation did not occur in the presence of iodide with either enzyme. Thus, both halides function in the MPO-H2O2 system but by different mechanisms. It is likely that in vivo under most conditions chloride is the functional halide and that generation of aldehydes is the mechanism responsible for the antimicrobial activity of the MPO-H2O2-chloride system.