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Anti‐transforming growth factor β‐induced protein antibody ameliorates vascular barrier dysfunction and improves survival in sepsis
Author(s) -
Bae J.S.,
Lee W.,
Son H.N.,
Lee Y.M.,
Kim I.S.
Publication year - 2014
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12398
Subject(s) - antibody , neutralizing antibody , sepsis , transforming growth factor , medicine , immunology , tgfbi , umbilical vein , vascular permeability , biology , biochemistry , in vitro
Aim Sepsis is a systemic inflammatory response syndrome resulting from a microbial infection. Transforming growth factor β‐induced protein ( TGFBI p) is an extracellular matrix protein expressed by human endothelial cells and platelets that induces sepsis through interaction with integrin αvβ5. The aim of this study was to investigate the role of TGFBI p in vascular permeability and the underlying mechanisms using TGFBI p‐neutralizing antibody. Methods Mice were subjected to caecal ligation and puncture (CLP) with or without neutralizing anti‐TGFBIp antibody (300 μ g kg −1 , intravenously). Wild‐type or integrin β5‐null mice received TGFBIp (0.1 mg kg −1 , intravenously) or were subjected to CLP. Human umbilical vein endothelial cells were exposed to lipopolysaccharide (100 ng mL −1 ) with or without neutralizing anti‐TGFBIp antibody (50 μ g mL −1 ). Results Administration of neutralizing anti‐ TGFBI p antibody in mice attenuated CLP ‐induced secretion of TGFBI p, leucocyte migration and vascular permeability and reduced septic mortality. Injected TGFBI p did not enhance vascular barrier permeability or leucocyte migration in β5‐null mice. Finally, neutralizing anti‐ TGFBI p antibody inhibited the specific interactions between TGFBI p and its receptor, integrin αvβ5. Conclusion Our findings demonstrate that treatment with a TGFBI p‐neutralizing antibody can ameliorate the deleterious effects of sepsis.