M. A. Zimmerman1, J. Kim1, A. Martin1, L. Fojut1, J. Yee1, J. C. Hong1 1Medical College Of Wisconsin,Transplant Surgery,Milwaukee, WI, USA
Introduction: Liver ischemia reperfusion injury (IRI) is a major cause of severe allograft dysfunction following orthotopic liver transplant. Innate immune responses contribute to hepatocellular injury following reperfusion. We hypothesize that the cross talk between neutrophils and natural killer cells (NK) plays an important role in tissue damage in hepatic IRI
Methods: A murine model of partial liver ischemia was initially employed using a hanging-weight system in 2 groups: C57Bl/6 and SCIDbeige (lack functional B and T lymphocytes, defective NK cell function). In addition, IRI was performed in a third group of SCIDbeige following neutrophil depletion (ND). All animals underwent 45 minutes of ischemia and 4 or 24 hours of reperfusion. Biochemical and histologic injury was assessed. Cytokine profiles were analyzed by reverse-transcription polymerase chain reaction (RT-PCR).
Results: Immunodeficient animals exhibit similar tissue injury compared to C57Bl6 (Figure 1A and B) at both 4 and 24 hours of reperfusion. ND in the setting of altered NK function exacerbates IRI compared to both C57Bl/6 of non-ND SCIDbeige (p<0.05). Injury in the non-ND SCIDbeige animals is associated with elevated interferon-g (IFNg), interleukin-10 (IL-10), and interleukin-6 (IL-6) expression (Figure 1C) (p<0.05).
Conclusion: Severe combined immunodeficiency does not protect the liver from IRI. Defective NK cell function is associated with elevated IFNg, IL-10, and IL-6 expression. Finally, neutrophil depletion, in the setting of altered NK function, exacerbates tissue injury as early as 4 hours following reperfusion.
