Artikel
Role of Lipocalin-2 in chemotaxis during ischemia and reperfusion injury following solid organ transplantation
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Autoren
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Felix Aigner
- Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
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Herbert Maier
- Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
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Stephan Sickinger
- Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
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Hubert Schwelberger
- Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
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Natalie Vallant
- Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
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Markus Kofler
- Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
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Stefan König
- Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
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Stefan Schneeberger
- Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
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Jakob Troppmair
- Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
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Johann Pratschke
- Univ.-Klinik für Visceral-, Transplantations- u. Thoraxchirurgie, Medizinische Universität Innsbruck, Department Operative Medizin, Innsbruck
| Veröffentlicht: | 20. Mai 2011 |
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Gliederung
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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.
