Jacobs W, Kumar-Singh S, Bogers J, Van de Vijver K, Deelder A, Van Marck E
Department of Pathology, University of Antwerp (U.I.A.), Universiteitsplein 1, B-2610 Antwerpen, Belgium.
Cell Tissue Res. 1998 Apr;292(1):101-6. doi: 10.1007/s004410051039.
In an attempt to elucidate further the immunopathological pathways that underlie fibrogenesis induced by Schistosoma mansoni, we have studied the distribution of basement membrane compounds, heparan sulphate proteoglycans (HSPG) and the fibrogenic cytokine transforming growth factor (TGF)-beta in two models of experimental schistosomiasis mansoni (experimental murine infection and synchronous granulomas induced by injection of egg-antigen-coupled beads into the caecal vein). Deposition of the basement membrane proteins type IV collagen, laminin and entactin in schistosomal granulomas was seen 3 days after the implantation of egg-antigen-coupled beads in the liver and persisted over time (32 days). Up-regulation of the membrane-bound HSPG syndecan-1 was observed in the schistosomal granuloma. These syndecan-1-immunoreactive cells represented a distinct subpopulation of granuloma cells; they were different from both mature, unstimulated B-cells (CD40-positive) and endothelial cells (CD105-positive). Deposition of the matrix HSPG perlecan within the granuloma was most prominent 8-16 days after injection. TGF-beta expression was observed in acute (8 weeks) and chronically (13 weeks) infected mice, mainly at the periphery of the schistosomal granuloma and on Kupffer cells in the liver parenchyma. From these observations, we infer that schistosomal fibrosis is composed of various groups of matrix components and that TGF-beta, which is secreted by granuloma cells, is one of the fibrogenic mediators in schistosomal fibrogenesis.
为了进一步阐明曼氏血吸虫诱导的纤维化形成的免疫病理途径，我们在两种曼氏血吸虫病实验模型（实验性小鼠感染以及通过将卵抗原偶联珠注入盲肠静脉诱导的同步肉芽肿）中研究了基底膜成分、硫酸乙酰肝素蛋白聚糖（HSPG）和促纤维化细胞因子转化生长因子（TGF）-β的分布。在将卵抗原偶联珠植入肝脏3天后，可见基底膜蛋白IV型胶原、层粘连蛋白和巢蛋白在血吸虫肉芽肿中的沉积，并随时间持续存在（32天）。在血吸虫肉芽肿中观察到膜结合HSPG syndecan-1的上调。这些syndecan-1免疫反应性细胞代表肉芽肿细胞的一个独特亚群；它们既不同于成熟的、未受刺激的B细胞（CD40阳性），也不同于内皮细胞（CD105阳性）。注射后8 - 16天，肉芽肿内基质HSPG核心蛋白聚糖的沉积最为显著。在急性（8周）和慢性（13周）感染的小鼠中均观察到TGF-β的表达，主要在血吸虫肉芽肿的周边以及肝实质中的库普弗细胞上。从这些观察结果中，我们推断血吸虫纤维化由各种基质成分组成，并且由肉芽肿细胞分泌的TGF-β是血吸虫纤维化形成中的促纤维化介质之一。
