Omura T
First Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
Hokkaido Igaku Zasshi. 1994 Sep;69(5):1220-31.
The distribution of ICAM-1/LFA-1-positive cells in rat liver grafts was investigated. The effect on graft survival of graft perfusion with anti-ICAM-1 monoclonal antibody before transplantation was also examined. Using ACI (RT-1av1) and LEW (RT-1(1)) inbred rats, orthotopic liver transplantation was performed both in allogeneic (ACI to LEW) and syngeneic (ACI to ACI) combinations. Transplanted liver tissues on days 2, 4 and 7 were immunohistochemically stained, using mouse anti-rat ICAM-1 monoclonal antibody (1A29, IgG1) and mouse anti-rat LFA-1 monoclonal antibody (WT-1, IgG2a). ACI livers perfused via portal vein with either 1A29, control antibody or lactate-Ringer's solution were transplanted to LEW recipients. ICAM-1 expression in normal ACI livers was confined to the endothelium of large portal vein and some central veins. A weak ICAM-1 expression was also observed on some sinusoidal endothelium. A small number of LFA-1-positive cells were resided in the normal liver. In allografted ACI livers, an intense ICAM-1 expression was induced on sinusoidal endothelium within 2 days after transplantation, and its expression was further increased on days 4 and 7. ICAM-1 expression on hepatocytes was also induced. LFA-1 positive infiltrates were gradually increased in number during the course of rejection, especially in the sinusoidal area. In the syngeneic combination, only a slight ICAM-1 induction on sinusoidal endothelium was observed. ICAM-1 upregulation on target structures of liver graft rejection suggests the importance of ICAM-1/LFA-1 in the pathogenesis of allograft rejection. Liver grafts perfused with anti-ICAM-1 monoclonal antibody were destroyed more rapidly than those perfused with control antibody or lactate-Ringer's solution both in allogeneic and syngeneic combinations. Histological examination revealed spotty ischemic necrosis in grafted liver. Perfusion with the antibody might cause the circulatory disturbance probably through the mechanism differing from alloantigen-specific response.
研究了大鼠肝移植中细胞间黏附分子-1（ICAM-1）/淋巴细胞功能相关抗原-1（LFA-1）阳性细胞的分布情况。还检测了移植前用抗ICAM-1单克隆抗体灌注移植物对移植物存活的影响。采用近交系大鼠ACI（RT-1av1）和LEW（RT-1(1)），进行了同种异体（ACI到LEW）和同基因（ACI到ACI）组合的原位肝移植。在术后第2、4和7天，使用小鼠抗大鼠ICAM-1单克隆抗体（1A29，IgG1）和小鼠抗大鼠LFA-1单克隆抗体（WT-1，IgG2a）对移植的肝组织进行免疫组织化学染色。将经门静脉灌注1A29、对照抗体或乳酸林格液的ACI肝脏移植给LEW受体。正常ACI肝脏中的ICAM-1表达局限于大的门静脉和一些中央静脉的内皮细胞。在一些肝窦内皮细胞上也观察到较弱的ICAM-1表达。正常肝脏中有少量LFA-1阳性细胞。在同种异体移植的ACI肝脏中，移植后2天内肝窦内皮细胞上诱导出强烈的ICAM-1表达，在第4天和第7天其表达进一步增加。肝细胞上也诱导出ICAM-1表达。在排斥反应过程中，LFA-1阳性浸润细胞数量逐渐增加，尤其是在肝窦区域。在同基因组合中，仅观察到肝窦内皮细胞上轻微的ICAM-1诱导。肝移植排斥反应靶结构上的ICAM-1上调提示ICAM-1/LFA-1在同种异体移植排斥发病机制中的重要性。在同种异体和同基因组合中，用抗ICAM-1单克隆抗体灌注的肝移植比用对照抗体或乳酸林格液灌注的肝移植破坏得更快。组织学检查显示移植肝脏有散在的缺血性坏死。抗体灌注可能通过不同于同种抗原特异性反应的机制导致循环障碍。
