Amelioration of sepsis by TIE2 activation-induced vascular protection

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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
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Issue Date
2016-04
Language
English
Article Type
Article
Keywords

MULTIPLE-ORGAN DYSFUNCTION; ACUTE LUNG INJURY; ENDOTHELIAL GLYCOCALYX; SEPTIC SHOCK; AGONIST PEPTIDE; TUMOR-GROWTH; ANGIOPOIETIN-1; ANGIOGENESIS; MORTALITY; LEAKAGE

Citation

SCIENCE TRANSLATIONAL MEDICINE, v.8, no.335

ISSN
1946-6234
DOI
10.1126/scitranslmed.aad9260
URI
http://hdl.handle.net/10203/209340
Appears in Collection
NT-Journal Papers(저널논문)MSE-Journal Papers(저널논문)
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