TY - JOUR
T1 - P-selectin glycoprotein ligand-1 (rPSGL-Ig)-mediated blockade of CD62 selectin molecules protects rat steatotic liver grafts from ischemia/reperfusion injury
AU - Amersi, Farin
AU - Farmer, Douglas G.
AU - Shaw, Gray D.
AU - Kato, Hirohisa
AU - Coito, Ana J.
AU - Kaldas, Fady
AU - Zhao, Delai
AU - Lassman, Charles R.
AU - Melinek, Judy
AU - Ma, Jeffrey
AU - Volk, Hans Dieter
AU - Kupiec-Weglinski, Jerzy W.
AU - Busuttil, Ronald W.
PY - 2002/8
Y1 - 2002/8
N2 - 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 Pselectin 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 TNFα, IL-6, iNOS, IL-2 and IFN-γ, 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.
AB - 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 Pselectin 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 TNFα, IL-6, iNOS, IL-2 and IFN-γ, 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.
KW - Hepatic steatosis, PSGL-1
KW - Reperfusion injury, selectin
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UR - http://www.scopus.com/inward/citedby.url?scp=0036705298&partnerID=8YFLogxK
U2 - 10.1034/j.1600-6143.2002.20704.x
DO - 10.1034/j.1600-6143.2002.20704.x
M3 - Article
C2 - 12201360
AN - SCOPUS:0036705298
VL - 2
SP - 600
EP - 608
JO - American Journal of Transplantation
JF - American Journal of Transplantation
SN - 1600-6135
IS - 7
ER -