COMP-Ang1 ameliorates leukocyte adhesion and reinforces endothelial tight junctions during endotoxemia |
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| Authors: | Jeong-Ah Hwang Eun Hui Lee Sang Do Lee Jin Bong Park Byeong Hwa Jeon Chung-Hyun Cho |
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| Institution: | 1. Department of Physiology, College of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-gu, Daejeon 301-131, Republic of Korea;2. Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea;3. From the Shanxi Medical University, Taiyuan 030001, China,;4. Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0575;5. Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0575;6. Research Services, Veterans Affairs Hospital and Department of Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0575;12. Department of Cardiology, Union Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China, and;9. Critical Illness Research, Lawson Health Research Institute, Ontario N6A 4G5, Canada;1. Graduate School of Biomedical Engineering, The University of New South Wales, Sydney, NSW 2052, Australia;2. HemCon Medical Technologies, Inc., Portland, OR, USA;1. School of Biological Sciences, Illinois State University, Normal, IL 61790, USA;2. Central Illinois Neuroscience Foundation, Bloomington, IL 61701, USA;1. Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan;2. Division of Integrated Surgery and Oncology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan;3. Division of International Cooperation for Disaster Medicine, International Research Institute of Disaster Science, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan;1. Department of Surgery, University of Virginia, Charlottesville, Virginia;2. Department of Pathology, University of Virginia, Charlottesville, Virginia |
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| Abstract: | Endotoxemia is characterized by multiple dysfunctions of the micro-vascular endothelium. Of these, vascular leakage is an initial event that aggravates vascular dysfunction can lead to systemic vascular collapse and organ failure. Thus, prevention of vascular leakage may ameliorate endotoxin-induced dysfunctions of blood vessels. Here we examine the effect of an angiopoietin-1 variant, COMP-Ang1, on endotoxin-induced vascular leakage in mice. COMP-Ang1 significantly reduced endotoxin-induced vascular leakage in the lung, heart, and kidney, but not in liver or intestine. Interestingly, COMP-Ang1 attenuated endotoxin-induced lung damage, presumably due to reduced infiltration of macrophages. Moreover, COMP-Ang1 restored the level of PECAM-1 expression, which is significantly reduced by endotoxin challenge. This study suggests that COMP-Ang1 reduces endotoxin-induced vascular leakage by restoration of cellular junctions and subsequent attenuation of leukocyte infiltration. |
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