P-selectin glycoprotein ligand-1 (rPSGL-Ig)-mediated blockade of CD62 selectin molecules protects rat steatotic liver grafts from ischemia/reperfusion injury.

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.

Amersi F ，Farmer DG ，Shaw GD ，Kato H ，Coito AJ ，Kaldas F ，Zhao D ，Lassman CR ，Melinek J ，Ma J ，Volk HD ，Kupiec-Weglinski JW ，Busuttil RW ... -  《AMERICAN JOURNAL OF TRANSPLANTATION》

A novel iron chelator in combination with a P-selectin antagonist prevents ischemia/reperfusion injury in a rat liver model.

Amersi F ，Dulkanchainun T ，Nelson SK ，Farmer DG ，Kato H ，Zaky J ，Melinek J ，Shaw GD ，Kupiec-Weglinski JW ，Horwitz LD ，Horwitz MA ，Busuttil RW ... -  《TRANSPLANTATION》

CD62 blockade with P-Selectin glycoprotein ligand-immunoglobulin fusion protein reduces ischemia-reperfusion injury after rat intestinal transplantation.

Farmer DG ，Shen XD ，Amersi F ，Anselmo D ，Ma JP ，Ke B ，Gao F ，Dry S ，Fernandez S ，Shaw GD ，McDiarmid SV ，Busuttil RW ，Kupiec-Weglinski J ... -  《TRANSPLANTATION》

Reduction of hepatic ischemia/reperfusion injury by a soluble P-selectin glycoprotein ligand-1.

Dulkanchainun TS ，Goss JA ，Imagawa DK ，Shaw GD ，Anselmo DM ，Kaldas F ，Wang T ，Zhao D ，Busuttil AA ，Kato H ，Murray NG ，Kupiec-Weglinski JW ，Busuttil RW ... -  《-》

Fibronectin-alpha 4 beta 1 integrin-mediated blockade protects genetically fat Zucker rat livers from ischemia/reperfusion injury.

Amersi F ，Shen XD ，Moore C ，Melinek J ，Busuttil RW ，Kupiec-Weglinski JW ，Coito AJ ... -  《-》