Comparison of inflammation, organ damage, and oxidant stress induced by Salmonella enterica serovar muenchen flagellin and serovar enteritidis lipopolysaccharide

L. Liaudet, K. G K Murthy, J. G. Mabley, P. Pacher, F. G. Soriano, A. L. Salzman, Csaba Szabo

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Gram-negative sepsis is related to the activation of interconnected inflammatory cascades in response to bacteria and their products. Recent work showed that flagellin, the monomeric subunit of bacterial flagella, triggers innate immune responses mediated by Toll-like receptor 5. Here, we compared the effects of Salmonella enterica serovar Enteritidis lipopolysaccharide (LPS) and recombinant Salmonella enterica serovar Muenchen flagellin administered intravenously (100 μg) to mice. Flagellin and LPS both elicited a prototypical systemic inflammatory response, with increased levels of tumor necrosis factor alpha, gamma interferon, interleukin 6 and 10, and nitrate in plasma. Flagellin induced a widespread oxidative stress, evidenced by an increase in malondialdehyde and a decrease in reduced glutathione in most organs, as well as liver (increased plasma aminotransferases), but not renal, injury. Alternatively, LPS resulted in a less severe oxidative stress and triggered renal, but not liver, damage. Sequestration of polymorphonuclear neutrophils (increased myeloperoxidase activity) in the lungs was observed with both toxins, while only LPS recruited neutrophils in the gut. In additional experiments, the simultaneous administration of small doses of LPS and flagellin (10 μg) induced a synergistic enhancement of the production of proinflammatory cytokines. Our data support a novel concept implicating flagellin as a mediator of systemic inflammation, oxidant stress, and organ damage induced by gram-negative bacteria.

Original languageEnglish (US)
Pages (from-to)192-198
Number of pages7
JournalInfection and Immunity
Volume70
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

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Flagellin
Salmonella enterica
Oxidants
Lipopolysaccharides
Inflammation
Oxidative Stress
Toll-Like Receptor 5
Neutrophils
Kidney
Inflammation Mediators
Salmonella enteritidis
Flagella
Liver
Transaminases
Malondialdehyde
Gram-Negative Bacteria
Innate Immunity
Interferon-alpha
Interleukin-10
Nitrates

ASJC Scopus subject areas

  • Immunology

Cite this

Comparison of inflammation, organ damage, and oxidant stress induced by Salmonella enterica serovar muenchen flagellin and serovar enteritidis lipopolysaccharide. / Liaudet, L.; Murthy, K. G K; Mabley, J. G.; Pacher, P.; Soriano, F. G.; Salzman, A. L.; Szabo, Csaba.

In: Infection and Immunity, Vol. 70, No. 1, 2002, p. 192-198.

Research output: Contribution to journalArticle

Liaudet, L. ; Murthy, K. G K ; Mabley, J. G. ; Pacher, P. ; Soriano, F. G. ; Salzman, A. L. ; Szabo, Csaba. / Comparison of inflammation, organ damage, and oxidant stress induced by Salmonella enterica serovar muenchen flagellin and serovar enteritidis lipopolysaccharide. In: Infection and Immunity. 2002 ; Vol. 70, No. 1. pp. 192-198.
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