Affordable Access

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

Authors
  • Bailie, M B
  • Standiford, T J
  • Laichalk, L L
  • Coffey, M J
  • Strieter, R
  • Peters-Golden, M
Type
Published Article
Journal
Journal of immunology (Baltimore, Md. : 1950)
Publication Date
Dec 15, 1996
Volume
157
Issue
12
Pages
5221–5224
Identifiers
PMID: 8955165
Source
Medline
License
Unknown

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.

Report this publication

Statistics

Seen <100 times