Flagellin from gram-negative bacteria is a potent mediator of acute pulmonary inflammation in sepsis

Details

Serval ID
serval:BIB_547ED4863F7F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Flagellin from gram-negative bacteria is a potent mediator of acute pulmonary inflammation in sepsis
Journal
Shock
Author(s)
Liaudet  L., Szabo  C., Evgenov  O. V., Murthy  K. G., Pacher  P., Virag  L., Mabley  J. G., Marton  A., Soriano  F. G., Kirov  M. Y., Bjertnaes  L. J., Salzman  A. L.
ISSN
1073-2322 (Print)
Publication state
Published
Issued date
02/2003
Volume
19
Number
2
Pages
131-7
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Feb
Abstract
Flagellin is a recently identified bacterial product that elicits immune response via toll-like receptor 5. Here, we demonstrate that flagellin is an extraordinarily potent proinflammatory stimulus in the lung during sepsis. In vitro, flagellin triggers the production of interleukin (IL)-8 by human lung epithelial (A549) cells, with 50% of the maximal response obtained at a concentration of 2 x 10(-14) M. Flagellin also induces the expression of ICAM-1 in vitro. Intravenous administration of flagellin to mice elicited a severe acute lung inflammation that was significantly more pronounced than following lipopolysaccharide (LPS) administration. Flagellin induced a local release of proinflammatory cytokines, the accumulation of inflammatory cells, and the development of pulmonary hyperpermeability. These effects were associated with the nuclear translocation of the transcription NF-kappaB in the lung. Flagellin remained active in inducing pulmonary inflammation at doses as low as 10 ng/mouse. In the plasma of patients with sepsis, flagellin levels amounted to 7.1 +/- 0.1 ng/mL. Plasma flagellin levels showed a significant positive correlation with the lung injury score, with the alveolar-arterial oxygen difference as well as with the duration of the sepsis. Flagellin emerges as a potent trigger of acute respiratory complications in gram-negative bacterial sepsis.
Keywords
Active Transport, Cell Nucleus Animals Cells, Cultured Chemokines/metabolism Dose-Response Relationship, Drug Flagellin/blood/*metabolism Gram-Negative Bacteria/*metabolism Humans Inflammation/*metabolism/microbiology Interleukin-1/blood Interleukin-8/metabolism Lipopolysaccharides/blood Lung/*immunology/metabolism/microbiology Macrophage Inflammatory Protein-1/blood Male Mice Mice, Inbred BALB C Monokines/blood NF-kappa B/metabolism Neutrophils/metabolism Nitric Oxide/metabolism Salmonella/metabolism Sepsis/*immunology/metabolism Time Factors Tumor Cells, Cultured
Pubmed
Web of science
Create date
24/01/2008 18:01
Last modification date
20/08/2019 15:09
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