The 150-Kilodalton Oxygen-Regulated Protein Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Mice

• Published in: The American journal of pathology Vol. 165; no. 4; pp. 1279 - 1288
• Main Authors: Nakagomi, Takayuki, Kitada, Osamu, Kuribayashi, Kozo, Yoshikawa, Hiroo, Ozawa, Kentaro, Ogawa, Satoshi, Matsuyama, Tomohiro
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.10.2004; ASIP; American Society for Investigative Pathology
• Subjects: Animals; Apoptosis - physiology; Biological and medical sciences; Blotting, Western; Bronchoalveolar Lavage Fluid - chemistry; Cells, Cultured; Disease Models, Animal; Female; HSP70 Heat-Shock Proteins; Immunohistochemistry; In Situ Nick-End Labeling; Investigative techniques, diagnostic techniques (general aspects); L-Lactate Dehydrogenase - metabolism; Lipopolysaccharides - pharmacology; Macrophages, Alveolar - metabolism; Medical sciences; Mice; Mice, Transgenic; Microscopy, Confocal; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Protein Biosynthesis; Proteins; Regular; Respiratory Distress Syndrome, Adult - chemically induced; Respiratory Distress Syndrome, Adult - pathology; Respiratory Mucosa - metabolism; Lung disease; Oxygen; Respiratory disease; Acute; Rodentia; Protein; Vertebrata; Anatomic pathology; Regulation(control); Mammalia; Mouse; Animal; Lipopolysaccharide
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)63387-1

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.