Martinez O M, Ascher N L, Ferrell L, Villanueva J, Lake J, Roberts J P, Krams S M
Department of Surgery, University of California, San Francisco 94143.
Transplantation. 1993 Apr;55(4):909-18. doi: 10.1097/00007890-199304000-00041.
The role of IL-5 and eosinophils in allograft rejection was studied in human liver allograft recipients. Liver allograft biopsies were analyzed for intragraft IL-5 gene expression, and the percentages of eosinophils and plasma cells within the portal infiltrate as well as peripheral eosinophil levels were determined. The majority of allografts with evidence of rejection had concomitant IL-5 mRNA and eosinophilia, while no resolving or nonrejecting allografts had simultaneous IL-5 mRNA and eosinophilia. In fact, rejecting liver allografts that contain IL-5 mRNA and eosinophils also contain infiltrating cells that produce the cytotoxic mediator major basic protein. In contrast, intragraft plasma cell and peripheral eosinophil levels did not correlate with the histopathologic status of the allograft. Cyclosporine and FK506 had similar effects on the frequency of IL-5 gene expression in rejecting and nonrejecting allografts. However, OKT3 appeared to profoundly modulate IL-5 gene expression, since 0 of 11 biopsies obtained during OKT3 treatment for rejection contained IL-5 transcripts. These observations raise the possibility of a cellular pathway of liver allograft rejection mediated by IL-5-activated eosinophils.
在人类肝移植受者中研究了白细胞介素-5(IL-5)和嗜酸性粒细胞在同种异体移植排斥反应中的作用。对肝移植活检组织进行分析,检测移植物内IL-5基因表达情况,并测定门管区浸润中嗜酸性粒细胞和浆细胞的百分比以及外周血嗜酸性粒细胞水平。大多数有排斥反应证据的移植物同时存在IL-5信使核糖核酸(mRNA)和嗜酸性粒细胞增多,而正在恢复或无排斥反应的移植物均未同时出现IL-5 mRNA和嗜酸性粒细胞增多。事实上,含有IL-5 mRNA和嗜酸性粒细胞的正在排斥的肝移植物中还含有产生细胞毒性介质主要碱性蛋白的浸润细胞。相比之下,移植物内浆细胞水平和外周血嗜酸性粒细胞水平与移植物的组织病理学状态无关。环孢素和他克莫司(FK506)对正在排斥和未排斥的移植物中IL-5基因表达频率的影响相似。然而,OKT3似乎能显著调节IL-5基因表达,因为在接受OKT3治疗排斥反应期间获取的11份活检组织中,有0份含有IL-5转录本。这些观察结果提示存在一条由IL-5激活的嗜酸性粒细胞介导的肝移植排斥反应细胞途径。