Prostaglandin E1 protects against ischemia-reperfusion injury of the liver by inhibition of neutrophil adherence to endothelial cells

Background This study investigates the protective mechanism of prostaglandin E-1 (PGE(1)) against hepatic ischemia-reperfusion injury in vivo, It has been demon strated that activated leukocytes contribute to ischemia-reperfusion injury, and that administration of the monoclonal antibody (mAb) for adhesion molecules reduces the injury by inhibiting leukocyte-endothelial cell adhesion, We therefore attempted to find out whether PGE(1) has an effect on the inhibition of neutrophil adherence to endothelial cells after reperfusion. Methods, We administered anti-intercellular adhesion molecule 1 (ICAM-1) mAb, antiserum against rat polymorphonuclear leukocytes, or PGE(1) to a rat model of left lobar ischemia for 60 min followed by reperfusion, Leukocyte adherence was observed by intravital fluorescence microscopy. The effect of PGE(1) on the expression of adhesion molecules was analyzed by immunohistochemistry and flow cytometry. Results. Ischemia-reperfusion caused endothelial dysfunction and hepatocellular injury with leukostasis in postsinusoidal venules. Anti-ICAM-1 mAb administration or leukopenia ameliorated both the hepatocellular injury and endothelial dysfunction, Although PGE(1) administration did not affect the serum interleukin-8 level, it significantly decreased hepatic injury and leukostasis in the reperfused liver. Immunohistochemical findings showed that PGE(1) decreased ICAM-1 expression on endothelial cells, but did not affect lymphocyte function-associated antigen 1, and membrane attack complex 1 on neutrophils in flow cytometric analysis, Conclusions. We conclude that PGE(1) protects the liver against ischemia reperfusion injury by reducing leukocyte-endothelial cell adhesion via down-medulation of ICAM-1 expression on the endothelium.