P‐Selectin Glycoprotein Ligand‐1 (rPSGL‐Ig)‐Mediated Blockade of CD62 Selectin Molecules Protects Rat Steatotic Liver Grafts from Ischemia/Reperfusion Injury
| Autor: | Farin Amersi, Douglas G. Farmer, Gray D. Shaw, Hirohisa Kato, Ana J. Coito, Fady Kaldas, Delai Zhao, Charles R. Lassman, Judy Melinek, Jeffrey Ma, Hans-Dieter Volk, Jerzy W. Kupiec-Weglinski, Ronald W. Busuttil |
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| Rok vydání: | 2002 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Ischemia Internal medicine medicine Animals Transplantation Homologous Immunology and Allergy Pharmacology (medical) Peroxidase Transplantation Membrane Glycoproteins business.industry Graft Survival Organ Preservation medicine.disease Liver Transplantation Rats Rats Zucker P-Selectin medicine.anatomical_structure Endocrinology Liver Reperfusion Injury Hepatocyte Immunology Cytokines Steatitis P-selectin glycoprotein ligand-1 Liver function business Reperfusion injury Ex vivo Selectin |
| Zdroj: | American Journal of Transplantation. 2:600-608 |
| ISSN: | 1600-6135 |
| Popis: | We examined the effects of early blockade of CD62 selectin-mediated adhesive interactions in steatotic rat liver models of ex vivo cold ischemia followed by reperfusion or transplantation by administration of P-selectin glycoprotein ligand-1 (rPSGL-Ig). In the model of cold ischemia/reperfusion, livers pretreated ex vivo with rPSGL-Ig at harvesting from obese Zucker rats showed significantly decreased portal resistance, increased bile production, and diminished hepatic endothelial neutrophil infiltration, as compared with untreated controls. Pretreatment of fatty livers with rPSGL-Ig prior to transplantation extended the survival of lean Zucker rat recipients from 40% to 90%. This effect correlated with significantly improved liver function, depressed neutrophil activity, and decreased histologic features of hepatocyte injury. Intragraft expression of CD62 P-selectin was similar in both recipient groups. rPSGL-Ig treatment decreased intragraft infiltration by CD3/CD25 cells, diminished expression of pro-inflammatory TNFalpha, IL-6, iNOS, IL-2 and IFN-gamma, without significantly affecting mRNA levels coding for anti-inflammatory IL-4. Thus, rPSGL-Ig blockade of CD62-mediated adhesive interactions protects against severe ischemia/reperfusion injury suffered otherwise by steatotic rat livers. These findings document the potential utility of rPSGL-Ig in increasing the transplant donor pool through modulation of marginal steatotic livers. |
| Databáze: | OpenAIRE |
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