Mac-1 (CD11b/CD18) and intercellular adhesion molecule-1 in ischemia-reperfusion injury of rat liver.

Abstract

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.

• Authors: A Kobayashi, H Imamura, M Isobe, Y Matsuyama, J Soeda, K Matsunaga, S Kawasaki
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 281 Issue 2 Pg. G577-85 (Aug 2001) ISSN: 0193-1857 [Print] United States
• PMID: 11447039 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acid Chloromethyl Ketones
• CD18 Antigens
• Caspase Inhibitors
• Cysteine Proteinase Inhibitors
• Macrophage-1 Antigen
• benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
• Intercellular Adhesion Molecule-1

Topics

• Amino Acid Chloromethyl Ketones (pharmacology)
• Animals
• Apoptosis
• CD18 Antigens (metabolism)
• Caspase Inhibitors
• Cell Nucleus (ultrastructure)
• Cysteine Proteinase Inhibitors (pharmacology)
• DNA Fragmentation
• Intercellular Adhesion Molecule-1 (metabolism)
• Kinetics
• Liver Diseases (metabolism, pathology)
• Macrophage-1 Antigen (metabolism)
• Male
• Necrosis
• Neutrophil Infiltration (drug effects)
• Rats
• Rats, Wistar
• Reperfusion Injury (metabolism, pathology)
• Survival Rate