title: COMP-Ang1 ameliorates leukocyte adhesion and reinforces endothelial tight junctions during endotoxemia.
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.
authors.affiliation: Department of Physiology, Chungnam National University, Jung-gu, Daejeon, Republic of Korea.
authors.forename: Jeong-Ah
authors.initials: JA
authors.lastname: Hwang
authors.forename: Eun Hui
authors.initials: EH
authors.lastname: Lee
authors.forename: Sang Do
authors.initials: SD
authors.lastname: Lee
authors.forename: Jin Bong
authors.initials: JB
authors.lastname: Park
authors.forename: Byeong Hwa
authors.initials: BH
authors.lastname: Jeon
authors.forename: Chung-Hyun
authors.initials: CH
authors.lastname: Cho
mesh_terms: D000818:Animals; D017209:Apoptosis; D019559:Capillary Leak Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D019446:Endotoxemia / Q000150:complications / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D007962:Leukocytes / Q000187:drug effects; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism
chemical_list: C515576:COMP-Ang1 fusion protein; D015815:Cell Adhesion Molecules; D008070:Lipopolysaccharides; D011993:Recombinant Fusion Proteins