Amelioration of sepsis by TIE2 activation-induced vascular protection

Title
Amelioration of sepsis by TIE2 activation-induced vascular protection
Authors
오승자Sangyeul HanSeung-Jun LeeKyung Eun KimHyo Seon LeeNuri OhInwon ParkEun KoYoon-Sook LeeDavid KimSeungjoo LeeDae Hyun LeeKwang-Hoon LeeSu Young ChaeSu-Jin KimHyung-Chan KimSeokkyun KimSung Hyun KimChungho KimYoshikazu NakaokaYulong HeHellmut G. AugustinJunhao HuPaul H. SongYong-In KimPilhan KimInjune KimGou Young KohJung-Hoon Lee
Issue Date
2016-04
Publisher
Science Translational Medicine
Citation
VOL 8, NO 335-335ra55-12
Abstract
Protection of endothelial integrity has been recognized as a frontline approach to alleviating sepsis progression, yet no effective agent for preserving endothelial integrity is available. Using an unusual anti-angiopoietin 2 (ANG2) antibody, ABTAA (ANG2-binding and TIE2-activating antibody), we show that activation of the endothelial receptor TIE2 protects the vasculature from septic damage and provides survival benefit in three sepsis mouse models. Upon binding to ANG2, ABTAA triggers clustering of ANG2, assembling an ABTAA/ANG2 complex that can subsequently bind and activate TIE2. Compared with a conventional ANG2-blocking antibody, ABTAA was highly effective in augmenting survival from sepsis by strengthening the endothelial glycocalyx, reducing cytokine storms, vascular leakage, and rarefaction, and mitigating organ damage. Together, our data advance the role of TIE2 activation in ameliorating sepsis progression and open a potential therapeutic avenue for sepsis to address the lack of sepsisspecific treatment.
URI
http://pubs.kist.re.kr/handle/201004/67159
ISSN
1946-6234
Appears in Collections:
KIST Publication > Article
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