Anti-transforming growth factor beta-induced protein antibody ameliorates vascular barrier dysfunction and improves survival in sepsis

Abstract

AimSepsis is a systemic inflammatory response syndrome resulting from a microbial infection. Transforming growth factor -induced protein (TGFBIp) is an extracellular matrix protein expressed by human endothelial cells and platelets that induces sepsis through interaction with integrin v5. The aim of this study was to investigate the role of TGFBIp in vascular permeability and the underlying mechanisms using TGFBIp-neutralizing antibody. MethodsMice were subjected to caecal ligation and puncture (CLP) with or without neutralizing anti-TGFBIp antibody (300gkg(-1), intravenously). Wild-type or integrin 5-null mice received TGFBIp (0.1mgkg(-1), intravenously) or were subjected to CLP. Human umbilical vein endothelial cells were exposed to lipopolysaccharide (100ngmL(-1)) with or without neutralizing anti-TGFBIp antibody (50gmL(-1)). ResultsAdministration of neutralizing anti-TGFBIp antibody in mice attenuated CLP-induced secretion of TGFBIp, leucocyte migration and vascular permeability and reduced septic mortality. Injected TGFBIp did not enhance vascular barrier permeability or leucocyte migration in 5-null mice. Finally, neutralizing anti-TGFBIp antibody inhibited the specific interactions between TGFBIp and its receptor, integrin v5. ConclusionOur findings demonstrate that treatment with a TGFBIp-neutralizing antibody can ameliorate the deleterious effects of sepsis.