Fibronectin-α4β1 integrin-mediated blockade protects genetically fat zucker rat livers from ischemia/reperfusion injury

Farin Amersi, Xiu Da Shen, Carolina Moore, Judy Melinek, Ronald W. Busuttil, Jerzy W. Kupiec-Weglinski, Ana J. Coito

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


We tested a hypothesis that interactions between fibronectin (FN), the major extracellular matrix component, and its integrin α4β1 receptor is important in the development of ischemia/reperfusion injury of steatotic liver transplants. We examined the effect of connecting segment-1 (CS1) peptide-facilitated blockade of FN-α4β1 interaction in a well-established steatotic rat liver model of ex vivo cold ischemia followed by iso-transplantation. In this model, CS1 peptides were administered through the portal vein of steatotic Zucker rat livers before and after cold ischemic storage. Lean Zucker recipients of fatty liver transplants received an additional 3-day course of CS1 peptides after transplant. CS1 peptide therapy significantly inhibited the recruitment of T lymphocytes, neutrophil activation/infiltration, and repressed the expression of proinflammatory tumor necrosis factor-α and interferon-γ. Moreover, it resulted in selective inhibition of inducible nitric oxide synthase expression, peroxynitrite formation, and hepatic necrosis. Importantly, CS1 peptide therapy improved function/histological preservation of steatotic liver grafts, and extended their 14-day survival in lean recipients from 40% in untreated to 100% in CS1-treated OLTs. Thus, CS1 peptide-mediated blockade of FN-α4β1 interaction protects against severe ischemia/reperfusion injury experienced otherwise by steatotic OLTs. These novel findings document the potential of targeting FN-α4β1 in vivo interaction to increase the transplant donor pool through modulation of marginal steatotic livers.

Original languageEnglish (US)
Pages (from-to)1229-1239
Number of pages11
JournalAmerican Journal of Pathology
Issue number4
StatePublished - Apr 1 2003

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


Dive into the research topics of 'Fibronectin-α4β1 integrin-mediated blockade protects genetically fat zucker rat livers from ischemia/reperfusion injury'. Together they form a unique fingerprint.

Cite this