IMPACT OF ADHESION MOLECULES OF THE SELECTIN FAMILY ON LIVER MICROCIRCULATION AT REPERFUSION FOLLOWING COLD ISCHEMIA

We investigated the role of adhesion molecules in the early phase of r eperfusion following cold ischemia. Livers of male Lewis rats were pre served for 0 h (group A) or 24 h in University of Wisconsin (UW) solut ion without additives (group B) or in UW solution with anti-ICAM-1 ant ibody (group C) or anti-E-selectin-1, SLe(x) and SLe(a) antibodies (gr oup D). The livers were then reperfused with diluted rat whole blood ( DWB; groups A and B), DWB containing anti-ICAM-1 and LFA-1 antibodies (group C) or DWB containing anti-l-selectin, SLe(x) and SLe(a) antibod ies (group D). The reperfusion was performed at 37 degrees C for 1 h a t 5 cm H2O of perfusion pressure. During reperfusion, hepatic microcir culation was assessed by monitoring portal and peripheral tissue blood flow. Bile production was significantly reduced in group B livers com pared with those in group A. Anti-ICAM-1 and LFA-1 antibodies failed t o improve hepatic microcirculation, whereas anti-LECAM-1, SLe(x) and S Le(a) antibodies significantly improved the microcirculation. Bile pro duction in group C and D livers was comparable to that in group B live rs. Preservation for 24 h significantly increased the release of TNF-a lpha from 0.207 to 43.7 pg/g per hour during reperfusion. Monoclonal a ntibodies to the adhesion molecules did not suppress the release of TN F-alpha in groups C and D. Histological examination demonstrated a lac k of leukocyte infiltration or thrombus in hetapic microvessels. The e xtent of hepatocyte necrosis did not differ among groups B, C, and D. We conclude that the microcirculatory disturbance in the early phase o f reperfusion occurs as a result of the tethering of leukocytes throug h the interaction of the selectin family and their ligands, and that t he ICAM-1-LFA-1 pathway is not involved in this step. The lack of impr ovement in bile production with antibodies to the selectin family and their ligands strongly suggests that other mechanisms participate in t he deterioration of hepatic function.