LEUKOCYTES CONTRIBUTE TO HEPATIC ISCHEMIA-REPERFUSION INJURY VIA INTERCELLULAR-ADHESION MOLECULE-1-MEDIATED VENULAR ADHERENCE

Background. Leukocytes are suggested to modulate ischemia/reperfusion injury via membrane receptor-controlled interaction with the microvascular endothelium. Methods. With the use of intravital fluorescence microscopy we investigated the role of the intercellular adhesion molecule-1 (ICAM-1) in a rat model of hepatic reperfusion injury with a neutralizing monoclonal antibody (anti-ICAM-1). Results. Sixty minutes of left lobar ischemia and reperfusion (isotype-matched immunoglobulin G(1) control antibody) caused leukostasis in sinusoids (240 +/- 15 cells per liver lobule), leukocyte adherence in postsinusoidal venules (679 +/- 76 cells per mm(2) endothelial surface of postsinusoidal venules), nutritive perfusion failure (15% +/- 2% nonperfused sinusoids), excretory dysfunction (bile flow, 1.2 +/- 0.3 mu l . min(-1) . gm(-1)), and loss of hepatocellular integrity (serum aspartate aminotransferase, 1353 +/- 317 units . L(-1); serum alanine aminotransferase, 1055 +/- 265 units . L(-1)). Anti-ICAM-1 did not affect sinusoidal leukostasis; however, it effectively inhibited postischemic leukocyte adherence to the venular endothelial living (217 +/- 38 cells/mm(2), p < 0.05). Concomitantly, hepatic reperfusion injury, including sinusoidal perfusion (6% +/- 1% nonperfused sinusoids, p < 0.01), excretory function (bile flow, 1.8 +/- 0.1 mu l . min(-1) . gm(-1), p < 0.05), and hepatocellular integrity (aspartate aminotransferase, 480 +/- 108 units . L(-1); alanine aminotransferase, 447 +/- 80 units . L(-1), p < 0.05), was significantly ameliorated by anti-ICAM-1. Conclusions. These findings prove in vivo the pivotal role of ICAM-1 in leukocyte-dependent manifestation of postischemic liver damage.