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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

MAC-1（CD11b/CD18）和细胞间粘附分子（ICAM-1）参与大鼠肝脏缺血再灌注损伤与肝窦内皮细胞损伤和肝细胞凋亡的关系

基本信息

批准号：
10671110
负责人：
IMAMURA Hiroshi
金额：
$ 2.37万
依托单位：
The University of Tokyo (1999)Shinshu University (1998)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671110/
关键词：
MAC-1 ICAM-1 neutrophil adhesion molecules transmigration apoptosis ischema-reperfusion injury 虚血再灌流障害 CD11b CD18(Mac-1)

项目摘要

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.

为探讨细胞间粘附分子1（ICAM- 1）和CD 11b/CD 18（Mac-1）在大鼠肝缺血/再灌注（I/R）中的相互作用，我们检测了这些分子的时序性表达谱、肝损伤的程度，包括肝窦内皮细胞（SEC）损伤和肝细胞凋亡，直到24小时，可逆性（30分钟）和致死性（60分钟）I/R。I/R 30 min时，神经细胞浸润和肝细胞坏死轻微且短暂，而I/R 60 min时，SEC数量减少，但在I/R 60 min时，SEC数量减少更为明显。然而，仅在60分钟的I/R Mac-1-中观察到肝细胞上ICAM-1的显著上调，显示出与肝损伤相似的尽管轻微的上调模式。肝细胞凋亡的时间分布和带状分布模式与肝损伤参数一致。结果表明：（1）中性粒细胞浸润参与了肝I/R损伤的发生和发展;（2）SEC上的ICAM-1与中性粒细胞上的Mac-1相互作用不是中性粒细胞通过内皮层的必要步骤，因为SEC在损伤早期是特异性受损的; 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是嗜中性粒细胞诱导的炎症和坏死反应的信号。