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PMID: 1908828 Published · ppublish English Journal Article

Staphylococcal exotoxins stimulate nitric oxide-dependent murine macrophage tumoricidal activity.

Infection and immunity ·Vol. 59 ·No. 9 ·1991-09-00 ·Pages 2987-93

Fast DJ, Shannon BJ, Herriott MJ, Kennedy MJ, Rummage JA, Leu RW

Abstract

The staphylococcal exotoxins toxic shock syndrome toxin 1 (TSST-1) and enterotoxin B were tested for their ability to stimulate murine peritoneal macrophages (PM) for tumoricidal activity. Both toxins were found to stimulate oil-elicited, gamma interferon-primed PM monolayers to kill nonadherent P815 tumor targets. The mechanism of killing of toxin-stimulated tumoricidal activity involved the production of nitric oxide, as nitrite could be demonstrated in culture fluids, and NG-monomethyl-L-arginine, an inhibitor of nitric oxide production, abrogated toxin-stimulated tumoricidal activity. TSST-1 stimulated the secretion of tumor necrosis factor by PM monolayers in the presence and absence of gamma interferon. The mechanism of toxin-stimulated tumoricidal activity was also determined to be independent of the production of reactive oxygen intermediates in that TSST-1 failed to stimulate H2O2 production by PM. These results demonstrate that the staphylococcal exotoxins are capable of stimulating macrophage production of nitric oxide for tumor cytotoxicity and suggest that the nitric oxide thus produced may subsequently play a role in the pathogenesis of the diseases caused by these toxins.

MeSH Terms
Animals Arginine/analogs & derivatives,pharmacology Bacterial Toxins Cytotoxicity, Immunologic Enterotoxins/pharmacology Hydrogen Peroxide/metabolism Interferon-gamma/pharmacology Lymphocyte Activation Macrophages/drug effects,immunology Male Mice Mice, Inbred C3H Nitric Oxide/antagonists & inhibitors,metabolism Staphylococcus aureus Superantigens Tumor Cells, Cultured/drug effects Tumor Necrosis Factor-alpha/biosynthesis omega-N-Methylarginine
Chemicals
Bacterial Toxins Enterotoxins Superantigens Tumor Necrosis Factor-alpha enterotoxin F, Staphylococcal omega-N-Methylarginine Nitric Oxide enterotoxin B, staphylococcal Interferon-gamma Arginine Hydrogen Peroxide
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Fast D J
Biomedical Division, Samuel Roberts Noble Foundation, Inc., Ardmore, Oklahoma 73402.
Shannon B J
Herriott M J
Kennedy M J
Rummage J A
Leu R W
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/iai.59.9.2987-2993.1991
Published
1991-09-00
Pages
2987-93
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC258123
Subset
IM
External Links
PubMed source DOI: 10.1128/iai.59.9.2987-2993.1991 PMC Full Text View journal details
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