Cytoplasts Generate Oxidants but Require Added Neutrophil Granule Constituents for Fungicidal Activity against Candida albicans Hyphae

Killing of Candida albicans hyphae requires oxidant generation by neutrophils (PMNL), but it is uncertain whether hyphal killing is mediated by PMNL oxidants alone or requires contributions by granule constituents. This was assessed using U-cytoplasts (U-CYT), anucleate PMNL fragments depleted of cy...

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Bibliographic Details
Published in:The Journal of infectious diseases 1995-08, Vol.172 (2), p.511-520
Main Authors: Stein, David K., Malawista, Stephen E., Van Blaricom, Gretchen, Wysong, Deborah, Diamond, Richard D.
Format: Article
Language:English
Subjects:
Antifungals
Biological and medical sciences
Candida albicans
Candida albicans - immunology
Cathepsin G
Cathepsins - pharmacology
Centrifugation
Cytoplasmic Granules - chemistry
Cytoplasmic Granules - immunology
Fluorescence
Fundamental and applied biological sciences. Psychology
Humans
Hydrogen Peroxide - metabolism
Hyphae
Hypochlorous Acid - metabolism
Lactoferrin - pharmacology
Major Articles
Microbiology
Mycology
Neutrophil Activation - drug effects
Neutrophils
Neutrophils - immunology
Opsonin Proteins - metabolism
Oxidants - metabolism
Oxidases
Pathogenicity, host-agent relations, miscellaneous strains, epidemiology
Peroxidase - pharmacology
Phagocytosis
Protease inhibitors
Respiratory Burst - drug effects
Serine Endopeptidases
Superoxides
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Summary:Killing of Candida albicans hyphae requires oxidant generation by neutrophils (PMNL), but it is uncertain whether hyphal killing is mediated by PMNL oxidants alone or requires contributions by granule constituents. This was assessed using U-cytoplasts (U-CYT), anucleate PMNL fragments depleted of cytoplasmic granules but retaining motility and respiratory burst activity. Granule-depleted U-CYT killed Staphylococcus aureus, but hyphae remained viable despite targeted generation of putatively fungicidal oxidants by avidly adherent U-CYT. Hyphal killing occurred by combining U-CYT with sublethal concentrations of purified PMNL granule extracts approximating those present in equivalent numbers of intact PMNL. Contributions of granule constituents were not entirely attributable to purified granule constituents with known antimicrobial activity (lactoferrin, cathepsin G, myeloperoxidase, and human neutrophil peptide defensins 1–3) individually or combined. Thus, oxidant generation by intact PMNL may be necessary but not always sufficient to mediate hyphal killing without complementary nonoxidative mechanisms.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/172.2.511