Inhibition by sulfonamides of the candidacidal activity of human neutrophils.

doi:10.1172/JCI106750

Paper

Inhibition by sulfonamides of the candidacidal activity of human neutrophils.

Published Dec 1, 1971 · R. Lehrer

The Journal of clinical investigation

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89

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1

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Abstract

Sulfonamides reduced substantially the ability of normal human neutrophils to kill strains of Candida albicans and Candida tropicalis, and impaired to a lesser extent their activity against Staphylococcus aureus 502A and Serratia marcescens. Sulfonamides also inhibited (a) iodination of Candida cells by normal neutrophils; (b) candidacidal activity in cell-free systems containing purified human myeloperoxidase, hydrogen peroxide, and potassium iodide; and (c) accumulation of molecular iodine in analogously constructed cell-free systems. In contrast to these effects on reactions catalyzed by myeloperoxidase, sulfonamides exerted relatively little effect on the levels of microbicidal activity manifested by human neutrophils that lacked myeloperoxidase. Sulfonamides appear to influence the function of human neutrophils predominantly by interfering with myeloperoxidase-mediated pathways. Certain basic and clinical implications of these data are discussed.

In Vitro Study

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Study Snapshot

Sulfonamides significantly reduce human neutrophils' ability to kill Candida albicans and Candida tropicalis, primarily by interfering with myeloperoxidase-mediated pathways.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Inhibition by sulfonamides of the candidacidal activity of human neutrophils.

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References

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The MPO-H2O2-chloride antimicrobial system generates aldehydes, which are responsible for the antimicrobial activity, with chloride being the functional halide under most conditions and aldehyde generation being the mechanism responsible for antimicrobial activity.

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Myeloperoxidase and intact normal leukocytes contribute significantly to the microbicidal activity of normal leukocytes, while peroxidase-negative leukocytes show less adaptation to azide-insensitive antimicrobial systems.

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Myeloperoxidase-deficient neutrophils and those from chronic granulomatous disease patients show limited candidacidal activity against Candida albicans, highlighting the need for targeted therapy.

Citations

Myeloperoxidase: Growing importance in cancer pathogenesis and potential drug target.

Myeloperoxidase plays a crucial role in cancer development and progression, and inhibiting it may be a promising strategy to fight against cancer.

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Reactive oxygen and nitrogen species play a crucial role in the innate immune system, fighting infections and contributing to human health and immunity.

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Myeloperoxidase (MPO) plays a dual role in immune response, aiding in microbe combating and potentially contributing to pathogenesis in diseases like cardiovascular diseases.

Anti-myeloperoxidase associated glomerulonephritis: a study of innate immune activation

Preventing macrophage infiltration did not significantly affect the development of ANCA-associated vasculitis in mice, suggesting a lesser role of macrophages in the disease or that disease was mild.

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The MPO system plays an important role in the microbicidal activity of phagocytes, but its toxic products may contribute to tissue injury.