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

J. S. Bae, W. Lee, H. N. Son, Y. M. Lee, In-San Kim

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Aim: 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. Conclusion: Our findings demonstrate that treatment with a TGFBIp-neutralizing antibody can ameliorate the deleterious effects of sepsis.

Original languageEnglish
Pages (from-to)306-315
Number of pages10
JournalActa Physiologica
Volume212
Issue number4
DOIs
Publication statusPublished - 2014 Dec 1
Externally publishedYes

Keywords

  • Caecal ligation and puncture
  • Leucocyte migration
  • Neutralizing antibody
  • Sepsis
  • Transforming growth factor β-induced protein
  • Vascular permeability

ASJC Scopus subject areas

  • Physiology

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