Enhanced expression of B7-1, B7-2, and intercellular adhesion molecule 1 in sinusoidal endothelial cells by warm ischemia/reperfusion injury in rat liver

To elucidate a role of costimulatory molecule and cell adhesion molecule in hepatic ischemia/reperfusion injury, we examined an alteration in B7-1 (CD 80), B7-2 (CD86), and intercellular adhesion molecule 1 (ICAM-1; CD54) expr ession in the rat liver after warm ischemia/reperfusion injury. To induce h epatic warm ischemia in a rat model, both portal vein and hepatic artery en tering the left-lateral and median lobes were occluded by clamping for 30 m inutes or 60 minutes, and then reperfused for 24 hours. B7-1, B7-2, and ICA M-1 expressions in the liver were analyzed by immunofluorescence staining a nd real-time reverse transcription polymerase chain reaction (RT-PCR). Alth ough B7-1 and B7-2 expressions were at very low levels in the liver tissues from normal or sham-operated control rats, both B7-1 and B7-2 expressions were enhanced at protein and messenger RNA (mRNA) levels in the affected, l eft lobes after warm ischemia/reperfusion. ICAM-1 protein and mRNA were con stitutively expressed in the liver of normal and sham-operated control rats , and further up-regulated after warm ischemia/reperfusion. Localization of increased B7-1, B7-2, and ICAM-1 proteins, as well as von Willebrand facto r as a marker protein for endothelial cells, was confined by immunofluoresc ence staining to sinusoidal endothelial cells in hepatic lobules. Data from quantitative real-time RT-PCR analysis revealed that B7-1 and B7-2 mRNA le vels were elevated in hepatic lobes after warm ischemia/reperfusion (5.13- and 52.9-fold increase, respectively), whereas ICAM-1 mRNA expression was r ather constitutive but further enhanced by warm ischemia/reperfusion (4.24- fold increase). These results suggest that hepatic sinusoidal endothelial c ells play a pivotal role as antigen-presenting cells by expressing B7-1 and B7-2 in warm hepatic ischemia/reperfusion injury, and that B7-1 and/or B7- 2 might be the primary target to prevent early rejection and inflammatory r eactions after hepatic ischemia/reperfusion injury associated with liver tr ansplantation.