FIBROBLAST STIMULATION IN SCHISTOSOMIASIS

该提案描述了作为项目的一部分的研究 理解细胞和分子网络的长期目标 参与调节慢性炎症的纤维化。是这样的 知识可能会提示预防疾病的药物策略 全身性疾病的病理性纤维化。 我们将在小鼠身上开发曼氏血吸虫感染的模型。在一个 评估肝卵肉芽肿巨噬细胞如何在 体内分泌刺激成纤维细胞的分子(迁移， 增殖和分泌基质蛋白)我们将确定小鼠T细胞 细胞杂交瘤来源的巨噬细胞激活因子(S)[MAF]可刺激 静止的巨噬细胞在体外分泌致纤维化物质。我们会 在1)肉芽肿培养中检测这种MAF活性 分离肉芽肿细胞悬液的上清液 富含T淋巴细胞；3)致敏脾细胞上清液 在体外用卵子抗原触发。我们还将测试 成纤维细胞直接刺激肉芽肿T细胞分泌淋巴因子 活动。生物活性物质的生化表征 物质将被执行。我们亦会特别注意 细胞因子刺激纤维连接蛋白分泌的能力 成纤维细胞。隐形细胞的一些生物学后果 纤维连接蛋白(巨噬细胞活化、成纤维细胞和单核/巨噬细胞 趋化性)将被研究。

This proposal describes studies which are part of a project with the long-term objectives of understanding the cellular and molecular network involved in regulating fibrosis complicating chronic inflammation. Such knowledge might suggest pharmacological strategies for preventing pathologic fibrosis in general diseases. We will exploit as a model Schistosoma mansoni infection in mice. In an effort to assess how hepatic egg granuloma macrophages become activated in vivo to secrete molecules which stimulate fibroblasts (to migrate, proliferate and secrete matrix proteins) we will determine whether murine T cell hybridoma-derived macrophage activating factor(s) [MAF] can stimulate quiescent macrophages in vitro to secrete fibrogenic substances. We will test for the presence of such MAF activity in 1) granuloma culture supernatants 2) supernatants from dissociated granuloma cell suspensions enriched for T lymphocytes, and 3) supernatants of sensitized spleen cells triggered in vitro with egg antigens. We will also test for the ability of granuloma T cells to secrete lymphokines with direct fibroblast-stimulating activity. Biochemical characterization of the biologically-active substances will be performed. Specific attention will also be given to the ability of the cytokines to stimulate fibronectin secretion by fibroblasts. Some of the biological consequences of the secreted fibronectin (macrophage activation and fibroblast and monocyte/macrophages chemotaxis) will be studied.