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 demonstrated 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 im-munohistochemistry 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 hepato-cellular 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. Immunohisto-chemical 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-modulation of ICAM-1 expression on the endothelium.