Diannexin, a novel annexin V homodimer, protects rat liver transplants against cold ischemia-reperfusion injury

X. D. Shen, B. Ke, Y. Zhai, S. I. Tsuchihashi, F. Gao, S. Duarte, A. Coito, R. W. Busuttil, A. C. Allison, J. W. Kupiec-Weglinski

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Ischemia/reperfusion injury (IRI) remains an important problem in clinical transplantation. Following ischemia, phosphatidylserine (PS) translocates to surfaces of endothelial cells (ECs) and promotes the early attachment of leukocytes/platelets, impairing microvascular blood flow. Diannexin, a 73 KD homodimer of human annexin V, binds to PS, prevents attachment of leukocytes/platelets to EC, and maintains sinusoidal blood flow. This study analyzes whether Diannexin treatment can prevent cold IRI in liver transplantation. Rat livers were stored at 4°C in UW solution for 24 h, and then transplanted orthotopically (OLT) into syngeneic recipients. Diannexin (200 μg/kg) was infused into: (i) donor livers after recovering and before reperfusion, (ii) OLT recipients at reperfusion and day +2. Controls consisted of untreated OLTs. Both Diannexin regimens increased OLT survival from 40% to 100%, depressed sALT levels, and decreased hepatic histological injury. Diannexin treatment decreased TNF-α, IL-1β, IP-10 expression, diminished expression of P-selectin, endothelial ICAM-1, and attenuated OLT infiltration by macrophages, CD4 cells and PMNs. Diannexin increased expression of HO-1/Bcl-2/Bcl-xl, and reduced Caspase-3/TUNEL+ apoptotic cells. Thus, by modulating leukocyte/platelet trafficking and EC activation in OLTs, Diannexin suppressed vascular inflammatory responses and decreased apoptosis. Diannexin deserves further exploration as a novel agent to attenuate IRI, and thereby improve OLT function/increase organ donor pool.

Original languageEnglish (US)
Pages (from-to)2463-2471
Number of pages9
JournalAmerican Journal of Transplantation
Volume7
Issue number11
DOIs
StatePublished - Nov 2007

Keywords

  • Adhesion molecules
  • Ischemia/reper-fusion injury
  • Liver transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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