gms | German Medical Science

128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

Role of Lipocalin-2 in chemotaxis during ischemia and reperfusion injury following solid organ transplantation

Meeting Abstract

  • Felix Aigner - Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
  • Herbert Maier - Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
  • Stephan Sickinger - Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
  • Hubert Schwelberger - Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
  • Natalie Vallant - Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
  • Markus Kofler - Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
  • Stefan König - Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
  • Stefan Schneeberger - Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
  • Jakob Troppmair - Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
  • Johann Pratschke - Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch564

DOI: 10.3205/11dgch564, URN: urn:nbn:de:0183-11dgch5648

Published: May 20, 2011

© 2011 Aigner et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Introduction: Neutrophil Gelatinase-associated Lipocalin (NGAL/Lcn-2) expression is associated with ischemia/reperfusion injury (IRI) following transplantation and correlates with polymorphonuclear cell infiltration. To get insight into the regulatory role of Lcn-2 during IRI the expression of different chemokines and adhesion molecules were analyzed in a murine heart transplantation model.

Materials and methods: The murine heterotopic heart transplant model also implying the Lcn-2-/- mouse with C57BL/6 background as well as primary cardiomyocytes and granulocytes were used for in vivo and in vitro experiments. The mRNA expression of the chemokines MIP-2, LIX, KC, MCP-1, IL-6 and CCL-6 and their receptors CXCR2 and CCR2 as well as ICAM-1 was analyzed by qPCR. Immunohistochemistry was performed in heart sections and correlated with neutrophil infiltration at various time points (2, 12, 24 and 48h). Recombinant Lcn-2 was labelled with FITC and uptake into target cells (COS-7, HL-1, HUVEC, MDCK) was analyzed by confocal fluorescence microscopy.

Results: Significant lower granulocyte infiltration and serum creatinine kinase levels during IRI were observed in the Lcn-2-/- transplants correlating with a stable ICAM-1 expression compared to the Lcn-2 wt setting (>5fold expression at 2h of reperfusion). In the early phase of reperfusion (2h) MCP-1, KC, LIX and MIP-2 showed a lower expression pattern in the Lcn-2-/- transplants with delayed upregulation at 12h (LIX, MIP-2). Uptake studies revealed that Lcn-2 is strongly internalized by cardiomyocytes and endothelial cells.

Conclusion: Our data point to a possible chemotactic role of Lcn-2 which may also affect the expression of particular chemokines in the early phase of IRI. The magnitude and kinetics of IRI influence Lcn-2 expression and susceptibility of various cell types in the reperfused myocardium. Understanding these regulatory mechanisms will be crucial to establish treatment strategies for IRI during solid organ transplantation.