Flagellin from Gram-Negative Bacteria is a Potent Mediator of Acute Pulmonary Inflammation in Sepsis.
Liaudet, Lucas *+++; Szabo, Csaba *+[S]; Evgenov, Oleg V. *[//]; Murthy, Kanneganti G. *; Pacher, Pal *; Virag, Laszlo *; Mabley, Jon G. *; Marton, Anita *; Soriano, Francisco G. *+; Kirov, Mikhail Y. [//][P]; Bjertnaes, Lars J. [//]; Salzman, Andrew L. *
19(2):131-137, February 2003.
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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-[kappa]B 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.
(C)2003The Shock Society