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Published on: March 29, 2017

Extracellular release of antimicrobial defensins by human polymorphonuclear leukocytes

T Ganz

    Infection and Immunity
    |March 1, 1987
    PubMed

    Insights

    Human neutrophils release antimicrobial defensins into extracellular spaces upon stimulation. Defensins are most effective in pus or phagolysosomes, not widely in circulation.

    Area of Science:

    • Immunology
    • Cell Biology
    • Microbiology

    Background:

    • Human polymorphonuclear leukocytes (PMN) possess antimicrobial and cytotoxic peptides known as defensins.
    • Defensins are crucial components of the innate immune system, involved in host defense against pathogens.

    Purpose of the Study:

    • To quantify the extracellular release of defensins from human PMN after stimulation.
    • To determine the potential of defensins for extracellular microbicidal or cytotoxic activities.

    Main Methods:

    • Human PMN were stimulated with phorbol myristate acetate and opsonized zymosan.
    • Extracellular defensin levels were measured using enzyme immunoassay.
    • Polyacrylamide gel electrophoresis and densitometry confirmed defensin quantification.
    • Release of granule markers (beta-glucuronidase, elastase, lactoferrin) and cytoplasmic marker (lactate dehydrogenase) were assessed.

    Main Results:

    • 10^6 human PMN contain 4-5 micrograms of defensins.
    • High-dose phorbol myristate acetate stimulation released approximately 8% of PMN defensins extracellularly.
    • Defensin release correlated with azurophil granule markers (beta-glucuronidase, elastase) but not specific granule markers (lactoferrin).
    • Phagocytosis of opsonized zymosan resulted in <3% extracellular defensin release.

    Conclusions:

    • Extracellular release of defensins from PMN is limited, suggesting restricted availability for systemic microbicidal activity.
    • Factors like granule heterogeneity and defensin-cell surface affinity may influence release.
    • Effective microbicidal concentrations of defensins are likely achieved in localized environments like pus, phagolysosomes, or intercellular clefts.

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