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 G1 control antibody) caused leukostasis in sinusoids (240 +/- 15 cells per liver lobule), leukocyte adherence in postsinusoidal venules (679 +/- 76 cells per mm2 endothelial surface of postsinusoidal venules), nutritive perfusion failure (15% +/- 2% nonperfused sinusoids), excretory dysfunction (bile flow, 1.2 +/- 0.3 microliters.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 lining (217 +/- 38 cells/mm2, p < 0.01). Concomitantly, hepatic reperfusion injury, including sinusoidal perfusion (6% +/- 1% nonperfused sinusoids, p < 0.01), excretory function (bile flow, 1.8 +/- 0.1 microliters.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.
Institute for Surgical Research, University of Munich, Germany.
B
B
Vollmar
J
J
Glasz
M D
MD
Menger
K
K
Messmer
D000818:Animals; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology*; D007962:Leukocytes / Q000502:physiology*; D008099:Liver / Q000098:blood supply*; D008297:Male; D008856:Microscopy, Fluorescence; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology* / Q000473:pathology; D014699:Venules / Q000473:pathology / Q000502:physiology
D018799:Intercellular Adhesion Molecule-1