Involvement of MAC-1 (CD11b/CD18) and intercellular adhesion molecule (ICAM-1) in the ischemia reperfusion injury of rat liver in relation to sinusoidal endothelial cell damage and hepatocyte apoptosis

为探讨细胞间黏附分子-1(ICAM-1)和CD11b/CD18(Mac-1)在大鼠肝脏缺血/再灌注(I/R)中的相互作用，我们观察了在可逆性(30min)和致死性(60min)两种情况下，肝组织中ICAM-1和CD11b/CD18(Mac-1)表达的时序性变化，包括肝窦内皮细胞(SEC)损伤和肝细胞凋亡。在I/R 60min时，两组SEC数量均随I/R时间延长而减少，但其幅度在I/R 60min时更为明显，但两组比较，ICAM-1上调SEC的程度与肝损伤程度呈负相关。然而，ICAM-1在肝细胞上的显著上调仅在I/R后60min观察到，其表达模式与肝损伤相似，但幅度较小。肝细胞凋亡的时间分布和带状分布与肝损伤参数的时间分布和带状分布一致。目前的资料表明，在肝脏I/R损伤中，1)中性粒细胞的滤过参与了中性粒细胞的发展；2)中性粒细胞表面的ICAM-1与中性粒细胞表面的Mac-1之间的相互作用不是中性粒细胞通过内皮细胞迁移的必要步骤，因为中性粒细胞在其早期阶段被特异性地损伤；3)中性粒细胞对ICAM-1和Mac-1的作用是其与肝细胞的牢固黏附和其功能激活；以及4)实质细胞的过度凋亡可能是中性粒细胞诱导的炎症和坏死反应的信号。

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.