Sakamoto S, Okanoue T, Itoh Y, Sakamoto K, Nishioji K, Nakagawa Y, Yoshida N, Yoshikawa T, Kashima K
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Hepatology. 1997 Sep;26(3):658-63. doi: 10.1053/jhep.1997.v26.pm0009303496.
The expression of several adhesion molecules is increased on the hepatic sinusoidal endothelial cells (SECs) in various liver diseases. The objective of this study is to assess the roles of intercellular adhesion molecule 1 (ICAM-1) and of CD18 in the interaction between the neutrophils (polymorphonuclear leukocytes [PMNs]) and SECs and in the injury to SECs mediated by PMNs. Rat PMNs was perfused on SECs stimulated with tumor necrosis factor alpha (TNF-alpha) using an in vitro flow system. The number of adhered PMNs to SECs and that of PMNs migrated under SECs was counted and the effects of anti-ICAM-1, anti-CD18, and dexamethasone were studied. We also define the effect of these antibodies on the SEC injury mediated by PMNs stimulated with phorbol 12-myristate 13-acetate (PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP). TNF-alpha significantly increased the adhesion of PMNs to SECs (322 +/- 26 cells/mm2) compared with controls (194 +/- 22 cells/mm2). Anti-ICAM-1 and anti-CD18 significantly inhibited the adhesion of PMNs (131 +/- 10 and 51 +/- 30 cells/mm2, respectively). These antibodies also decreased the migration rate of PMNs (6.0% and 7.9%, respectively) compared with controls (migration rate, 21.2%). The SEC injury induced by PMA- and fMLP-activated PMNs was prevented by anti-ICAM-1 and anti-CD18. The adhesion of PMNs induced by TNF-alpha was inhibited by the treatment with dexamethasone (160 +/- 20 cells/mm2) via a down-regulation of ICAM-1 expression on SECs. The interactions between ICAM-1 and CD18 appeared to be important in the adhesion and the migration of PMNs to SECs. The injury to SECs was induced by the close interaction between the activated PMNs and SECs mediated via ICAM-1 and CD18.
在各种肝脏疾病中，肝窦内皮细胞（SECs）上几种黏附分子的表达会增加。本研究的目的是评估细胞间黏附分子1（ICAM-1）和CD18在中性粒细胞（多形核白细胞[PMNs]）与SECs相互作用以及PMNs介导的SECs损伤中的作用。使用体外流动系统，将大鼠PMNs灌注到用肿瘤坏死因子α（TNF-α）刺激的SECs上。计算黏附于SECs的PMNs数量以及在SECs下方迁移的PMNs数量，并研究抗ICAM-1、抗CD18和地塞米松的作用。我们还确定了这些抗体对由佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）或N-甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）刺激的PMNs介导的SECs损伤的影响。与对照组（194±22个细胞/mm²）相比，TNF-α显著增加了PMNs与SECs的黏附（322±26个细胞/mm²）。抗ICAM-1和抗CD18显著抑制了PMNs的黏附（分别为131±10和51±30个细胞/mm²）。与对照组（迁移率为21.2%）相比，这些抗体也降低了PMNs的迁移率（分别为6.0%和7.9%）。抗ICAM-1和抗CD18可预防由PMA和fMLP激活的PMNs诱导的SECs损伤。地塞米松处理通过下调SECs上ICAM-1的表达抑制了TNF-α诱导的PMNs黏附（160±20个细胞/mm²）。ICAM-1和CD18之间的相互作用似乎在PMNs与SECs的黏附和迁移中起重要作用。活化的PMNs与SECs通过ICAM-1和CD18介导的紧密相互作用诱导了SECs的损伤。
