COMP-Ang1 ameliorates leukocyte adhesion and reinforces endothelial tight junctions during endotoxemia.
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.
Hwang
Jeong-Ah
JA
Department of Physiology, Chungnam National University, Jung-gu, Daejeon, Republic of Korea.
Lee
Eun Hui
EH
Lee
Sang Do
SD
Park
Jin Bong
JB
Jeon
Byeong Hwa
BH
Cho
Chung-Hyun
CH
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
C515576:COMP-Ang1 fusion protein; D015815:Cell Adhesion Molecules; D008070:Lipopolysaccharides; D011993:Recombinant Fusion Proteins