The 150-kilodalton oxygen-regulated protein ameliorates lipopolysaccharide-induced acute lung injury in mice.
The 150-kd oxygen-regulated protein is a novel stress protein that is located in the endoplasmic reticulum and contributes to cell survival when this organelle is under stress. Expression of this protein was strongly increased in alveolar macrophages and alveolar epithelial cells from mice with acute lung injury induced by lipopolysaccharide. Transgenic mice overexpressing the 150-kd protein showed decreased histological severity of this lung injury, accompanied by lower total protein concentrations, and lactate dehydrogenase activity in bronchoalveolar lavage fluid. As indicated by nick end-labeling, lipopolysaccharide induced apoptosis in fewer alveolar wall cells in transgenic than in wild-type mice. Transgenic mice also showed increased survival after lipopolysaccharide injection (a log-rank test). Thus, the 150-kd protein, an endoplasmic reticulum-related molecular chaperone, is pivotal in resisting acute lung injury from lipopolysaccharide.
Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. nakagomi@hyo-med.ac.jp.
Takayuki
T
Nakagomi
Osamu
O
Kitada
Kozo
K
Kuribayashi
Hiroo
H
Yoshikawa
Kentaro
K
Ozawa
Satoshi
S
Ogawa
Tomohiro
T
Matsuyama
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D018840:HSP70 Heat-Shock Proteins; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D014176:Protein Biosynthesis; D011506:Proteins; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000473:pathology*; D020545:Respiratory Mucosa / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D008070:Lipopolysaccharides; D011506:Proteins; C050087:oxygen-regulated proteins; D007770:L-Lactate Dehydrogenase