CD11c+ cells are required to prevent progression from local acute lung injury to multiple organ failure and death.
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.
Milam
Jami E
JE
VA Ann Arbor Healthcare System, Ann Arbor, MI 48105, USA.
Erb-Downward
John R
JR
Chen
Gwo-Hsiao
GH
Osuchowski
Marcin F
MF
McDonald
Roderick
R
Chensue
Stephen W
SW
Toews
Galen B
GB
Huffnagle
Gary B
GB
Olszewski
Michal A
MA
D055371:Acute Lung Injury / Q000097:blood / Q000150:complications* / Q000201:enzymology / Q000473:pathology*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D001806:Blood Urea Nitrogen; D039521:CD11c Antigen / Q000378:metabolism*; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004167:Diphtheria Toxin / Q000494:pharmacology; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D009102:Multiple Organ Failure / Q000097:blood / Q000150:complications* / Q000201:enzymology / Q000473:pathology*; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D012995:Solubility / Q000187:drug effects; D016019:Survival Analysis
D015415:Biomarkers; D039521:CD11c Antigen; D016207:Cytokines; D004167:Diphtheria Toxin; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase