Yamaguchi Y, Ichiguchi O, Matsumura F, Akizuki E, Matsuda T, Okabe K, Yamada S, Liang J, Mori K, Ogawa M
Department of Surgery II, Kumamoto University Medical School, Honjo, Japan.
Hepatology. 1997 Dec;26(6):1546-52. doi: 10.1053/jhep.1997.v26.pm0009397996.
The kinetics of messenger RNA (mRNA) and protein levels of cytokine-induced neutrophil chemoattractant (CINC) in rat hepatic allografts during acute rejection were investigated. Infiltrating cells were identified by double immunostaining with anti-CINC and anti-macrophage monoclonal antibodies, ED1 and ED2. The serum CINC concentration in untreated hepatic allograft recipients increased significantly at a constant rate over time after transplantation. No significant increases in serum CINC concentrations were observed in hepatic isografts or allografts treated with the immunosuppressant FK506. The number of neutrophils in untreated hepatic allografts increased significantly at a constant rate. Conversely, neutrophil accumulation in isografts or allografts treated with FK506 was much less than in untreated hepaticallografts. Immunostaining revealed that in the portal areas, mononuclear cells infiltrating untreated allograft liver were mainly positive for CINC and that CINC+ cells represented a subpopulation (approximately 25%) of the ED1+ cells. On the other hand, in the sinusoidal areas CINC+ cells were scattered and mainly positive for ED2. Levels of CINC mRNA in liver tissues taken from untreated hepatic allografts increased after transplantation, peaked on day 5, and decreased thereafter. Hepatic allografts treated with FK506 or isografts showed much lower levels of CINC mRNA than untreated allografts. Allogeneic mixed lymphocyte reactions induced CINC production. The cellular source of CINC was mononuclear cells. CINC production in mixed lymphocyte reactions was inhibited in the presence of anti-tumor necrosis factor alpha (TNF-alpha) antibody. These results suggest that enhanced expression of CINC mRNA and prominent accumulation of neutrophils in the liver grafts are characteristic features of the immune response during acute rejection.
研究了大鼠肝脏同种异体移植急性排斥反应期间，细胞因子诱导的中性粒细胞趋化因子（CINC）的信使核糖核酸（mRNA）和蛋白质水平的动力学变化。通过用抗CINC和抗巨噬细胞单克隆抗体ED1和ED2进行双重免疫染色来鉴定浸润细胞。未治疗的肝脏同种异体移植受体血清CINC浓度在移植后随时间以恒定速率显著增加。在肝脏同基因移植或用免疫抑制剂FK506治疗的同种异体移植中，未观察到血清CINC浓度有显著增加。未治疗的肝脏同种异体移植中中性粒细胞数量以恒定速率显著增加。相反，用FK506治疗的同基因移植或同种异体移植中的中性粒细胞积聚比未治疗的肝脏同种异体移植少得多。免疫染色显示，在门管区，浸润未治疗同种异体移植肝脏的单核细胞主要为CINC阳性，且CINC+细胞占ED1+细胞亚群（约25%）。另一方面，在肝血窦区，CINC+细胞呈散在分布，主要为ED2阳性。从未治疗的肝脏同种异体移植获取的肝组织中CINC mRNA水平在移植后升高，在第5天达到峰值，随后下降。用FK506治疗的肝脏同种异体移植或同基因移植显示出比未治疗的同种异体移植低得多的CINC mRNA水平。同种异体混合淋巴细胞反应诱导CINC产生。CINC的细胞来源是单核细胞。在存在抗肿瘤坏死因子α（TNF-α）抗体的情况下，混合淋巴细胞反应中的CINC产生受到抑制。这些结果表明，CINC mRNA表达增强和肝移植中中性粒细胞显著积聚是急性排斥反应期间免疫反应的特征性表现。
