Mac-1 (CD11b/CD18) and intercellular adhesion molecule-1 in ischemia-reperfusion injury of rat liver.
The chronological expression (over 24 h) of two adhesion molecules [intercellular adhesion molecule-1 (ICAM-1) and CD11b/CD18 (Mac-1)] and the extent of liver damage, including injury to sinusoidal endothelial cells (SECs) and hepatocyte apoptosis, were investigated under two conditions of rat liver ischemia-reperfusion (I/R) injury: reversible (30 min) and fatal I/R (60 min). The chronological profiles of upregulation of ICAM-1 on hepatocytes and Mac-1 showed changes in parallel with the other liver damage parameters, and the extent of upregulation and various parameters of liver injury were more advanced in the 60-min I/R group. Paradoxically, the degree of ICAM-1 upregulation of SECs decreased significantly in the 60-min I/R group vs. the 30-min I/R group. Repression of hepatocyte apoptosis by administration of the caspase inhibitor ZVAD-fmk resulted in attenuation of neutrophil infiltration and liver injury. These findings indicate that 1) neutrophil infiltration is involved in the development of liver I/R injury; 2) interaction between ICAM-1 on SECs and Mac-1 on neutrophils is not an essential step for neutrophil transmigration through the endothelial layer because SECs, specifically, were impaired in the early stages of liver I/R injury; 3) the role of ICAM-1 and Mac-1 is to adhere neutrophils firmly to hepatocytes and activate neutrophils; and 4) excessive parenchymal apoptosis may be the signal for the neutrophil-induced inflammatory and necrotic reaction.
Kobayashi
A
A
First Department of Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Imamura
H
H
Isobe
M
M
Matsuyama
Y
Y
Soeda
J
J
Matsunaga
K
K
Kawasaki
S
S
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D018821:CD18 Antigens / Q000378:metabolism*; D061945:Caspase Inhibitors; D002467:Cell Nucleus / Q000648:ultrastructure; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007700:Kinetics; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D008297:Male; D009336:Necrosis; D020556:Neutrophil Infiltration / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate
D000590:Amino Acid Chloromethyl Ketones; D018821:CD18 Antigens; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D016177:Macrophage-1 Antigen; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D018799:Intercellular Adhesion Molecule-1