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Leukotriene-deficient mice manifest enhanced lethality from Klebsiella pneumonia in association with decreased alveolar macrophage phagocytic and bactericidal activities.

M B Bailie, T J Standiford, L L Laichalk, M J Coffey, R Strieter and M Peters-Golden
J Immunol December 15, 1996, 157 (12) 5221-5224;
M B Bailie
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T J Standiford
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L L Laichalk
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M J Coffey
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R Strieter
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M Peters-Golden
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Abstract

Leukotrienes (LTs) are potent mediators of inflammation derived from the 5-lipoxygenase pathway of arachidonic acid metabolism. Although they are known to enhance leukocyte recruitment and function, their role in antimicrobial host defense has not been established. To determine the role of endogenous LTs in the host response to pulmonary infection, wild-type mice and mice rendered LT-deficient by targeted disruption of the 5-lipoxygenase gene (knockout mice) were studied following intratracheal challenge with Klebsiella pneumoniae. Wild-type mice demonstrated a marked increase in lung LT levels and neutrophil numbers following bacterial challenge. As compared with wild-type animals, knockout animals manifested a greater degree of lethality as well as bacteremia following challenge. Interestingly, they displayed no defect in neutrophil recruitment to the lung. However, alveolar macrophages from knockout animals exhibited impairments in bacterial phagocytosis and killing, and these defects were overcome by in vitro addition of exogenous LTB4. We conclude that endogenous LTs play a critical role in the defense against bacterial pneumonia in this murine model.

  • Copyright © 1996 by American Association of Immunologists

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The Journal of Immunology
Vol. 157, Issue 12
15 Dec 1996
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Leukotriene-deficient mice manifest enhanced lethality from Klebsiella pneumonia in association with decreased alveolar macrophage phagocytic and bactericidal activities.
M B Bailie, T J Standiford, L L Laichalk, M J Coffey, R Strieter, M Peters-Golden
The Journal of Immunology December 15, 1996, 157 (12) 5221-5224;

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Leukotriene-deficient mice manifest enhanced lethality from Klebsiella pneumonia in association with decreased alveolar macrophage phagocytic and bactericidal activities.
M B Bailie, T J Standiford, L L Laichalk, M J Coffey, R Strieter, M Peters-Golden
The Journal of Immunology December 15, 1996, 157 (12) 5221-5224;
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Print ISSN 0022-1767        Online ISSN 1550-6606