Protection of sinusoidal endothelial cells against storage/reperfusion injury by prostaglandin E-2 derived from Kupffer cells

Background. In clinical liver transplants, grafts are frequently exposed to endotoxin (lipopolysaccharide, LPS) before harvest and may be predisposed to dysfunction. Because graft failure is linked to sinusoidal endothelial c ell injury after storage/reperfusion, we investigated the effect of donor e xposure to LPS on graft survival in relation to sinusoidal endothelial cell injury after storage/reperfusion in rats. Methods. Rats were injected with 0.5 mg/kg LPS. In some rats, 20 mg/kg GdCl 3 or 5 mg/kg indomethacin was injected before LPS to ablate Kupffer cells a nd inhibit prostaglandin (PG) synthesis, respectively. Other rats were inje cted with 100 mu g/kg dimethyl PGE(2), a stable PGE(2) analog. Rat livers w ere harvested, stored in cold UW solution and transplanted to non-treated r ats for determination of survival and liver injury in recipients. Otherwise , after cold storage, the livers were reperfused briefly with physiological buffer containing trypan blue for determination of sinusoidal endothelial cell injury by counting trypan blue-positive nuclei in histological section s. Results. Donor treatment with LPS increased hepatic PGE(2) production befor e storage and decreased recipient survival, but paradoxically decreased kil ling of sinusoidal endothelial cells after storage and reperfusion. Pretrea tment of donors with GdCl3 or indomethacin prevented the protective precond itioning of sinusoidal endothelial cells by LPS, whereas pretreatment with dimethyl PGE(2) protected sinusoidal endothelial cells to the same extent a s LPS. Unlike LPS, however, PGE(2) attenuated graft injury after liver tran splants. Conclusion. PGE(2) derived from LPS-stimulated Kupffer cells protects sinus oidal endothelial cells against storage/reperfusion injury. Unlike LPS, PGE (2) improves graft function after liver transplants. Thus, donor preconditi oning with PGE(2) may be beneficial in liver transplants.