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Russo, T.A. et al.

Thomas A. Russo, Bruce A. Davidson, Janet M. Beanan, Ruth Olson, Bruce A. Holm, Robert H. Notter, Paul R. Knight,

Capsule and O-antigen from an extraintestinal isolate of Escherichia coli modulate cytokine levels in rat macrophages in vitro and in a rat model of pneumonia.

Gram-negative pneumonia results in significant morbidity, mortality, and cost to the healthcare system. Previously the authors demonstrated that capsule and O-antigen, virulence factors of the extraintestinal Escherichia coli isolate CP9, modulate pulmonary neutrophil influx in a rat pneumonia model. In this report, the authors utilized CP9 and mutants deficient in O-antigen (CP921), capsule (CP9.137), or both (CP923) to test the hypothesis that modulation of cytokine levels by capsule and/or O-antigen may be a contributory mechanism. Effects of capsule and O-antigen on cytokine levels in rats in vivo and in isolated pulmonary macrophages in vitro were assessed. In vivo, capsule and O-antigen had no significant effect on tumor necrosis factor (TNF)-alpha levels in bronchoalveolar lavage fluid (BALF), but both were associated with significant increases in the levels of interleukin (IL)-1beta and Cytokine-induced neutrophil Chemoattractant-1 (CINC-1). However, potential difficulties in interpreting data occurred because challenge bacterial strains exhibited differential growth, and clearance characteristics and mixed cell populations were present. Therefore, added mechanistic studies investigated specific interactions of capsule and O-antigen with pulmonary macrophages purified from normal rats and exposed to CP9, CP921, CP9.137, or CP923 in vitro. Results indicated that the presence of capsule led to significantly increased levels of TNF-alpha, IL-1beta, and CINC-1, whereas O-antigen significantly decreased macrophage-associated levels of these mediators. These findings support the hypothesis that CP9 capsule is proinflammatory for macrophage-induced neutrophil recruitment, whereas O-antigen attenuates macrophage production of proinflammatory mediators in pneumonia. These results expand our understanding on the mechanisms by which these virulence traits may contribute to the inflammatory pathogenesis of pneumonia.[1]

References

Capsule and O-antigen from an extraintestinal isolate of Escherichia coli modulate cytokine levels in rat macrophages in vitro and in a rat model of pneumonia. Russo, T.A., Davidson, B.A., Beanan, J.M., Olson, R., Holm, B.A., Notter, R.H., Knight, P.R. Exp. Lung Res. (2007) [Pubmed]

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