Abstract
To investigate the role of CD11c(+) cells in endotoxin-induced acute lung injury, wild-type or CD11c-diphtheria toxin receptor transgenic mice were treated with intraperitoneal diphtheria toxin (5 ng/g b.wt.) in the presence or absence of intratracheal lipopolysaccharide (51 microg). Lipopolysaccharide treatment resulted in 100% mortality in CD11c-depleted animals but not in control animals. Analysis of local lung tissue revealed no differences in acute lung injury severity; however, analysis of distal tissues revealed severe damage and necrosis to multiple organs (liver, spleen, and kidneys) in CD11c-diphtheria toxin receptor mice but not in wild-type mice. In addition, dramatic increases in systemic levels of liver enzymes (alanine aminotransferase, 657 U/L, aspartate aminotransferase, 1401 U/L), blood urea (53 mg/dl), and 8-iso-prostaglandin F(2alpha), a marker of oxidative stress (350 pg/ml), were observed. These data demonstrate that CD11c(+) cells play a critical role in protecting the organs from systemic injury caused by a pulmonary endotoxin challenge.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Acute Lung Injury / blood
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Acute Lung Injury / complications*
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Acute Lung Injury / enzymology
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Acute Lung Injury / pathology*
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Alanine Transaminase / blood
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Animals
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Aspartate Aminotransferases / blood
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Biomarkers / metabolism
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Blood Urea Nitrogen
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CD11c Antigen / metabolism*
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Capillaries / drug effects
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Capillaries / pathology
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Cytokines / genetics
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Cytokines / metabolism
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Diphtheria Toxin / pharmacology
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Disease Models, Animal
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Disease Progression
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Gene Expression Regulation
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Heparin-binding EGF-like Growth Factor
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Intercellular Signaling Peptides and Proteins / metabolism
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Kidney / drug effects
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Kidney / pathology
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Lipopolysaccharides
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Mice
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Mice, Inbred C57BL
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Multiple Organ Failure / blood
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Multiple Organ Failure / complications*
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Multiple Organ Failure / enzymology
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Multiple Organ Failure / pathology*
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Necrosis
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Oxidative Stress / drug effects
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Pulmonary Alveoli / blood supply
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Pulmonary Alveoli / drug effects
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Pulmonary Alveoli / pathology
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Solubility / drug effects
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Survival Analysis
Substances
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Biomarkers
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CD11c Antigen
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Cytokines
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Diphtheria Toxin
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Hbegf protein, mouse
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Heparin-binding EGF-like Growth Factor
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Intercellular Signaling Peptides and Proteins
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Lipopolysaccharides
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Aspartate Aminotransferases
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Alanine Transaminase