Abstract | RATIONALE: OBJECTIVES: METHODS: Wild-type (WT) and MFG-E8(-/-) mice underwent superior mesenteric artery occlusion for 90 minutes, followed by reperfusion for 4 hours. A group of WT mice was treated with 0.4 microg/20 g recombinant murine MFG-E8 (rmMFG-E8) at the beginning of reperfusion. Four hours after reperfusion, MFG-E8, cytokines, myeloperoxidase activity, apoptosis, and histopathology were assessed. A 24-hour survival study was conducted in rmMFG-E8- and vehicle-treated WT mice. MEASUREMENTS AND MAIN RESULTS: Mesenteric I/R caused severe widespread injury and inflammation of the small intestines and remote organs, including the lungs. MFG-E8 levels decreased in the spleen and lungs by 50 to 60%, suggesting impaired apoptotic cell clearance. Treatment with rmMFG-E8 significantly suppressed inflammation ( TNF-alpha, IL-6, IL-1beta, and myeloperoxidase) and injury of the lungs, liver, and kidneys. MFG-E8-deficient mice suffered from greatly increased inflammation and potentiated ALI, whereas treatment with rmMFG-E8 significantly improved the survival in WT mice. CONCLUSIONS: MFG-E8 attenuates inflammation and ALI after gut I/R and may represent a novel therapeutic agent.
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Authors | Tianpen Cui, Michael Miksa, Rongqian Wu, Hidefumi Komura, Mian Zhou, Weifeng Dong, Zhimin Wang, Shinya Higuchi, Wayne Chaung, Steven A Blau, Corrado P Marini, Thanjavur S Ravikumar, Ping Wang |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 181
Issue 3
Pg. 238-46
(Feb 01 2010)
ISSN: 1535-4970 [Electronic] United States |
PMID | 19892861
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Antigens, Surface
- Biomarkers
- Mfge8 protein, mouse
- Milk Proteins
- RNA
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Topics |
- Acute Lung Injury
(etiology, genetics, metabolism)
- Animals
- Antigens, Surface
(biosynthesis, genetics, therapeutic use)
- Biomarkers
- Blotting, Western
- Disease Models, Animal
- Disease Progression
- Gene Expression Regulation
- Intestinal Diseases
(complications, metabolism)
- Male
- Mice
- Mice, Inbred C57BL
- Milk Proteins
(biosynthesis, genetics, therapeutic use)
- RNA
(genetics)
- Reperfusion Injury
(complications, metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
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