Amelioration of sepsis by TIE2 activation-induced vascular protection

被引：159

作者：

Han, Sangyeul ^{[1
,2
]}

Lee, Seung-Jun ^{[2
,3
]}

Kim, Kyung Eun ^{[1
,10
]}

Lee, Hyo Seon ^{[1
,10
]}

Oh, Nuri ^{[3
]}

Park, Inwon ^{[4
]}

Ko, Eun ^{[1
,10
]}

Oh, Seung Ja ^{[1
,11
]}

Lee, Yoon-Sook ^{[1
,10
]}

Kim, David ^{[3
]}

Lee, Seungjoo ^{[3
]}

Lee, Dae Hyun ^{[3
]}

Lee, Kwang-Hoon ^{[1
,12
]}

Chae, Su Young ^{[1
,10
]}

Lee, Jung-Hoon ^{[1
,10
]}

Kim, Su-Jin ^{[1
,10
]}

Kim, Hyung-Chan ^{[1
,10
]}

Kim, Seokkyun ^{[1
,10
]}

Kim, Sung Hyun ^{[1
,13
]}

Kim, Chungho ^{[5
]}

Nakaoka, Yoshikazu ^{[6
]}

He, Yulong ^{[7
]}

Augustin, Hellmut G. ^{[8
,9
]}

Hu, Junhao ^{[8
]}

Song, Paul H. ^{[1
,10
]}

Kim, Yong-In ^{[1
,14
]}

Kim, Pilhan ^{[4
]}

Kim, Injune ^{[3
]}

Koh, Gou Young ^{[2
,3
]}

机构：

[1] Samsung Adv Inst Technol, Suwon 446712, South Korea

[2] Inst for Basic Sci Korea, Ctr Vasc Res, Taejon 305701, South Korea

[3] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Taejon 305701, South Korea

[4] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol, Taejon 305701, South Korea

[5] Korea Univ, Sch Life Sci & Technol, Seoul 136701, South Korea

[6] Osaka Univ, Grad Sch Med, Dept Cardiovasc Med, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan

[7] Soochow Univ, Cyrus Tang Hematol Ctr, Suzhou 215123, Peoples R China

[8] German Canc Res Ctr Heidelberg DKFZ ZMBH Alliance, Div Vasc Oncol & Metastasis, D-69121 Heidelberg, Germany

[9] Heidelberg Univ, Med Fac Mannheim, Dept Vasc Biol & Tumor Angiogenesis CBIM, D-68167 Mannheim, Germany

[10] Samsung Bioepis, Inchon 406712, South Korea

[11] Samsung Elect Co Ltd, Samsung Biomed Res Inst, Suwon 446712, South Korea

[12] Osong Med Innovat Fdn, New Drug Dev Ctr, Cheongju 363951, South Korea

[13] Korea Inst Ceram Engn & Technol, Seoul 153801, South Korea

[14] Medytox, Pangyo Bioresearch Ctr, Songnam 463410, South Korea

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2016年 / 8卷 / 335期

关键词：

MULTIPLE-ORGAN DYSFUNCTION; ENDOTHELIAL GLYCOCALYX; LUNG INJURY; AGONIST PEPTIDE; TUMOR-GROWTH; ANGIOPOIETIN-1; ANGIOGENESIS; MORTALITY; COMP-ANG1; ANTIBODY;

D O I：

10.1126/scitranslmed.aad9260

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：11

共 70 条

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