|Budget Amount *help
¥3,700,000 (Direct Cost : ¥3,700,000)
Fiscal Year 1999 : ¥1,600,000 (Direct Cost : ¥1,600,000)
Fiscal Year 1998 : ¥2,100,000 (Direct Cost : ¥2,100,000)
To investigate the mutual involvement of intercellular adhesion molecule 1 (ICAM- 1) and CD11b/CD18 (Mac-1) in rat liver ischemia/reperfusion (I/R), we examined the chronological expression profiles of these molecules, the extent of liver damage including sinusoidal endothelial cells (SEC) injury and hepatocyte apoptosis until 24 hr in two conditions, i.e., reversible (30 min) and fatal (60 min) I/R. Neutrophil infiltration and hepatocellular necrosis was minimal and transient in 30 min of I/R ; while it was progressing in 60 min of I/R SEC number was decreased following I/R in both groups, although its extent was more marked in 60 min of I/R The extent of ICAM-1 up-regulation on SEC was inversely correlated with that of liver injury when two groups were compared. Whereas, marked up-regulation of ICAM-1 on hepatocytes was observed solely in 60 min of I/R Mac-1-showed a similar, albeit mild, up-regulation patterns as that of liver injury. Chronological profiles and zonal distribution pattern of hepatocyte apoptosis demonstrated a coincidence with those of parameters liver damage. The present data indicate that, in liver I/R injury, 1) neutrophil iufiltration is involved in its development, 2) interaction between ICAM-1 on SEC and Mac- 1on neutrophil is not an essential step for the neutrophil transmigration through the endothelial layer since SEC was specifically impaired in its early stage ; 3) The role of ICAM-1 and Mac-1 for the neutrophil is in its firm adherence to hepatocyte and its functional activation; and 4) excessive parenchymal apoptosis may represent a signal for neutrophil-induced inflammatory and necrotic reaction.