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

Lucas Liaudet, Csaba Szabó, Oleg V. Evgenov, Kanneganti G. Murthy, Pál Pacher, László Virág, Jon G. Mabley, Anita Marton, Francisco G. Soriano, Mikhail Y. Kirov, Lars J. Bjertnaes, Andrew L. Salzman

    Research output: Contribution to journalArticle

    92 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)131-137
    Number of pages7
    JournalShock (Augusta, Ga.)
    Volume19
    Issue number2
    DOIs
    StatePublished - Feb 2003

    ASJC Scopus subject areas

    • Emergency Medicine
    • Critical Care and Intensive Care Medicine

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  • Cite this

    Liaudet, L., Szabó, C., Evgenov, O. V., Murthy, K. G., Pacher, P., Virág, L., Mabley, J. G., Marton, A., Soriano, F. G., Kirov, M. Y., Bjertnaes, L. J., & Salzman, A. L. (2003). Flagellin from gram-negative bacteria is a potent mediator of acute pulmonary inflammation in sepsis. Shock (Augusta, Ga.), 19(2), 131-137. https://doi.org/10.1097/00024382-200302000-00008