title: Anti-transforming growth factor β-induced protein antibody ameliorates vascular barrier dysfunction and improves survival in sepsis.
abstract: OBJECTIVE
  Sepsis is a systemic inflammatory response syndrome resulting from a microbial infection. Transforming growth factor β-induced protein (TGFBIp) 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 TGFBIp in vascular permeability and the underlying mechanisms using TGFBIp-neutralizing antibody.
  
  
  METHODS
  Mice were subjected to caecal ligation and puncture (CLP) with or without neutralizing anti-TGFBIp antibody (300 μg 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 μg mL(-1)).
  
  
  RESULTS
  Administration 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 β5-null mice. Finally, neutralizing anti-TGFBIp antibody inhibited the specific interactions between TGFBIp and its receptor, integrin αvβ5.
  
  
  CONCLUSIONS
  Our findings demonstrate that treatment with a TGFBIp-neutralizing antibody can ameliorate the deleterious effects of sepsis.
authors.affiliation: College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Korea; BK21 Plus KNU Biomedical Convergence Program, Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.
authors.forename: J-S
authors.initials: JS
authors.lastname: Bae
authors.forename: W
authors.initials: W
authors.lastname: Lee
authors.forename: H-N
authors.initials: HN
authors.lastname: Son
authors.forename: Y-M
authors.initials: YM
authors.lastname: Lee
authors.forename: I-S
authors.initials: IS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D002199:Capillary Permeability / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019030:Receptors, Vitronectin / Q000276:immunology*; D018805:Sepsis / Q000276:immunology* / Q000628:therapy*; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D019030:Receptors, Vitronectin; D016212:Transforming Growth Factor beta; C064660:integrin alphaVbeta5
keywords: caecal ligation and puncture; leucocyte migration; neutralizing antibody; sepsis; transforming growth factor β-induced protein; vascular permeability