白细胞通过细胞间黏附分子-1介导的小静脉黏附作用导致肝缺血/再灌注损伤。

Leukocytes contribute to hepatic ischemia/reperfusion injury via intercellular adhesion molecule-1-mediated venular adherence.

作者信息

Vollmar B, Glasz J, Menger M D, Messmer K

机构信息

Institute for Surgical Research, University of Munich, Germany.

出版信息

Surgery. 1995 Feb;117(2):195-200. doi: 10.1016/s0039-6060(05)80085-6.

DOI:10.1016/s0039-6060(05)80085-6

PMID:7846625

Abstract

BACKGROUND

Leukocytes are suggested to modulate ischemia/reperfusion injury via membrane receptor-controlled interaction with the microvascular endothelium.

METHODS

With the use of intravital fluorescence microscopy we investigated the role of the intercellular adhesion molecule-1 (ICAM-1) in a rat model of hepatic reperfusion injury with a neutralizing monoclonal antibody (anti-ICAM-1).

RESULTS

Sixty minutes of left lobar ischemia and reperfusion (isotype-matched immunoglobulin G1 control antibody) caused leukostasis in sinusoids (240 +/- 15 cells per liver lobule), leukocyte adherence in postsinusoidal venules (679 +/- 76 cells per mm2 endothelial surface of postsinusoidal venules), nutritive perfusion failure (15% +/- 2% nonperfused sinusoids), excretory dysfunction (bile flow, 1.2 +/- 0.3 microliters.min-1.gm-1), and loss of hepatocellular integrity (serum aspartate aminotransferase, 1353 +/- 317 units.L-1; serum alanine aminotransferase, 1055 +/- 265 units.L-1). Anti-ICAM-1 did not affect sinusoidal leukostasis; however, it effectively inhibited postischemic leukocyte adherence to the venular endothelial lining (217 +/- 38 cells/mm2, p < 0.01). Concomitantly, hepatic reperfusion injury, including sinusoidal perfusion (6% +/- 1% nonperfused sinusoids, p < 0.01), excretory function (bile flow, 1.8 +/- 0.1 microliters.min-1.gm-1, p < 0.05), and hepatocellular integrity (aspartate aminotransferase, 480 +/- 108 units.L-1; alanine aminotransferase, 447 +/- 80 units.L-1, p < 0.05), was significantly ameliorated by anti-ICAM-1.

CONCLUSIONS

These findings prove in vivo the pivotal role of ICAM-1 in leukocyte-dependent manifestation of postischemic liver damage.

摘要

背景

有研究表明白细胞可通过膜受体控制的与微血管内皮细胞的相互作用来调节缺血/再灌注损伤。

方法

利用活体荧光显微镜，我们用一种中和性单克隆抗体（抗ICAM - 1）研究了细胞间黏附分子 - 1（ICAM - 1）在大鼠肝脏再灌注损伤模型中的作用。

结果

左叶缺血60分钟后再灌注（同型匹配的免疫球蛋白G1对照抗体）导致肝血窦白细胞淤滞（每肝小叶240±15个细胞）、肝血窦后小静脉白细胞黏附（肝血窦后小静脉每平方毫米内皮表面679±76个细胞）、营养性灌注衰竭（15%±2%的血窦未灌注）、排泄功能障碍（胆汁流量，1.2±0.3微升·分钟-1·克-1）以及肝细胞完整性丧失（血清天冬氨酸转氨酶，1353±317单位·升-1；血清丙氨酸转氨酶，1055±265单位·升-1）。抗ICAM - 1不影响血窦白细胞淤滞；然而，它有效抑制了缺血后白细胞对小静脉内皮的黏附（217±38个细胞/平方毫米，p<0.01）。同时，抗ICAM - 1显著改善了肝脏再灌注损伤，包括血窦灌注（6%±1%的血窦未灌注，p<0.01）、排泄功能（胆汁流量，1.8±0.1微升·分钟-1·克-1，p<0.05）以及肝细胞完整性（天冬氨酸转氨酶，480±108单位·升-1；丙氨酸转氨酶，447±80单位·升-1，p<0.05）。