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PMID: 2659536 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Tumor necrosis factor alpha potentiates neutrophil antimicrobial activity: increased fungicidal activity against Torulopsis glabrata and Candida albicans and associated increases in oxygen radical production and lysosomal enzyme release.

Infection and immunity ·Vol. 57 ·No. 7 ·1989-07-00 ·Pages 2115-22

Ferrante A

Abstract

The capacity of human tumor necrosis factor alpha (TNF-alpha) to modulate the killing of the opportunistic pathogens Torulopsis glabrata and Candida albicans by human neutrophils was studied. TNF-alpha significantly enhanced neutrophil fungicidal activity in a concentration-dependent manner and was evident in a range of neutrophil-fungus ratios. Enhanced killing of T. glabrata required much lower TNF-alpha concentrations than were required for enhancement of killing of C. albicans. Maximal enhancement of killing occurred with 20 and 100 U of TNF-alpha per 5 x 10(6) neutrophils for T. glabrata and C. albicans, respectively. The fungal killing kinetics demonstrated that TNF-alpha augmentation of fungicidal activity was evident within 1 h and persisted for an incubation period of at least 22 h. Preincubation of neutrophils with TNF-alpha was essential for the enhancement of killing. Maximal stimulation of killing was observed within 1 h of preincubation with TNF-alpha, and poor stimulation of killing was observed when TNF-alpha was added at time zero. Associated with the increase in fungicidal activity was an increased production of superoxide and an enhanced degranulation of enzymes and other proteins from azurophilic and specific granules in response to the fungi. The results demonstrate that TNF-alpha augments the neutrophil oxidative respiratory burst and the degranulation induced by opsonized fungi and that it increases the neutrophil fungicidal activity.

MeSH Terms
Adjuvants, Immunologic/toxicity Antifungal Agents/toxicity Blood Bactericidal Activity Candida/immunology Candida albicans/immunology Cytotoxicity, Immunologic Dose-Response Relationship, Immunologic Free Radicals Humans Lysosomes/enzymology Neutrophils/enzymology,immunology,microbiology Oxygen Consumption Time Factors Tumor Necrosis Factor-alpha/toxicity
Chemicals
Adjuvants, Immunologic Antifungal Agents Free Radicals Tumor Necrosis Factor-alpha
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Ferrante A
Department of Immunology, Adelaide Children's Hospital, Australia.
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/iai.57.7.2115-2122.1989
Published
1989-07-00
Pages
2115-22
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC313849
Subset
IM
External Links
PubMed source DOI: 10.1128/iai.57.7.2115-2122.1989 PMC Full Text View journal details
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