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

为了研究细胞间粘附分子 1 (ICAM-1) 和 CD11b/CD18 (Mac-1) 在大鼠肝脏缺血/再灌注 (I/R) 中的相互参与，我们检查了这些分子的时间顺序表达谱、肝脏损伤的程度，包括窦状内皮细胞 (SEC) 损伤和肝细胞凋亡，直至 24 小时，两种情况即可逆性（30 分钟）和致命性（60 分钟） I/R。在 I/R 30 分钟内，中性粒细胞浸润和肝细胞坏死很少且短暂；而在 I/R 60 分钟内进展，两组 I/R 后 SEC 数量均下降，尽管其程度在 I/R 60 分钟内更为明显。两组比较时，SEC 上 ICAM-1 上调的程度与肝损伤程度呈负相关。然而，仅在 I/R Mac-1 的 60 分钟内观察到肝细胞上 ICAM-1 的显着上调，显示出与肝损伤相似但轻微的上调模式。肝细胞凋亡的时间分布和区域分布模式与肝损伤参数一致。目前的数据表明，在肝I/R损伤中，1）中性粒细胞滤过参与其发展，2）SEC上的ICAM-1和中性粒细胞上的Mac-1之间的相互作用并不是中性粒细胞通过内皮层迁移的必要步骤，因为SEC在早期阶段就受到了特别的损害； 3）ICAM-1和Mac-1对中性粒细胞的作用在于其与肝细胞的牢固粘附和功能激活； 4）过度的实质细胞凋亡可能代表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.