INHIBITION OF LEUKOCYTE ADHERENCE AND TRANSENDOTHELIAL MIGRATION IN CULTURED HUMAN LIVER VASCULAR ENDOTHELIAL-CELLS BY PROSTAGLANDIN E-1

Primary graft dysfunction is a major complication of orthotopic liver transplantation, and hepatic ischemic reperfusion injury is considered to be its major determinant cause. Although oxygen free radicals play an important role, leukocytes, cytokines, and adhesion molecules also contribute to hepatic ischemic reperfusion injury. Prostaglandin E-1 (PGE(1)) has been shown to protect against impairment and dysfunction of transplanted livers in various experimental models as well as in cl inical liver transplantation. In this study, the role of PGE(1) on leu kocyte adherence and transendothelial migration was investigated in cu ltured human liver vascular endothelial cells (HLVEC). Our results ind icated that stimulated, but not resting, leukocytes exhibited high adh esion and transmigration capacity, HLVEC incubated with tumor necrosis factor (TNF) promoted leukocyte adherence and transendothelial migrat ion, PGE(1) inhibited leukocyte adherence to HLVEC when it was preincu bated with either HLVEC or leukocytes, Moreover, PGE(1) also suppresse d stimulated leukocyte transendothelial migration in a dose-dependent manner, The inhibitory activity of PGE(1) was further investigated on both HLVEC and leukocytes with attention to adhesion molecules, On HLV EC, PGE(1) down-regulated TNF-induced expression of endothelial cell l eukocyte adhesion molecule 1 and vascular adhesion molecule 1, but not intercellular adhesion molecule 1, On leukocytes, PGE(1) inhibited ex pression of CD11a/CD18 and membrane-bound TNF on PHA-stimulated leukoc ytes, PGE, also suppressed TNF release from the stimulated leukocytes, These results indicated that inhibition of leukocyte adherence and tr ansendothelial migration is one of the mechanisms by which PGE(1) prot ects liver grafts.