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Increased airspace epithelial permeability is an early event in lung inflammation and injury. In this study, we have developed a rat model to study the mechanisms of the epithelial permeability to 125iodine-labeled bovine serum albumin (125I-BSA), instilled intratracheally during acute lung inflammation. Epithelial permeability was measured as the percentage of instilled 125I-BSA appearing in the blood. The increase in epithelial permeability induced by intratracheal instillation of heat-killed Corynebacterium parvum produced a peak influx of neutrophils into the bronchoalveolar space at 16 h, which occurred after the peak increase in epithelial permeability (8 h). The increased epithelial permeability induced by C. parvum did not appear to be protease- or oxidant-mediated. Depletion of peripheral blood neutrophils was achieved by an intravenous injection of anti-neutrophil polyclonal antibody. The consequent profound reduction in neutrophil and macrophage influx into the airspaces 8 h after instillation of C. parvum reduced the epithelial permeability to control values. Bronchoalveolar lavage (BAL) leukocytes from rats 8 h, but not 16 h, after treatment with C. parvum caused a modest increase in epithelial permeability when re-instilled intratracheally into control rat lungs. Separation of the leukocytes before re-instillation indicated that macrophages rather than neutrophils were predominantly responsible for the increased epithelial permeability. The presence of dramatically increased levels of tumor necrosis factor (TNF) in BAL 8 h in contrast to a slight increase in BAL 16 h after C. parvum, the release of TNF from 8 h macrophages, the increased epithelial permeability induced by TNF in epithelial monolayers in vitro, and the inhibition of C. parvum-induced epithelial permeability by TNF antibody support the premise that TNF is a major player in the increased epithelial permeability that occurs during C. parvum-induced acute alveolitis.
X Y Li, and
K Donaldson, and
D Brown, and
W MacNee
April 2011,
European journal of pharmacology,
X Y Li, and
K Donaldson, and
D Brown, and
W MacNee
June 1988,
The American review of respiratory disease,
X Y Li, and
K Donaldson, and
D Brown, and
W MacNee
May 2005,
The European respiratory journal,
X Y Li, and
K Donaldson, and
D Brown, and
W MacNee
January 2005,
Oftalmologia (Bucharest, Romania : 1990),
X Y Li, and
K Donaldson, and
D Brown, and
W MacNee
November 1988,
The American review of respiratory disease,
X Y Li, and
K Donaldson, and
D Brown, and
W MacNee
January 1989,
Critical care clinics,
X Y Li, and
K Donaldson, and
D Brown, and
W MacNee
April 1998,
Gastroenterology,
X Y Li, and
K Donaldson, and
D Brown, and
W MacNee
December 1987,
The Journal of laboratory and clinical medicine,
X Y Li, and
K Donaldson, and
D Brown, and
W MacNee
December 1998,
American journal of respiratory cell and molecular biology,
X Y Li, and
K Donaldson, and
D Brown, and
W MacNee
January 2013,
Journal of vascular research,
