FIBROBLAST STIMULATION IN SCHISTOSOMIASIS

血吸虫病中的成纤维细胞刺激

• 批准号: 3566214
• 负责人: DAVID J WYLER
• 金额: $ 17.79万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3566214
• 关键词: Schistosoma mansoni; T lymphocyte; affinity chromatography; autoradiography; cell biology; cell growth regulation; chemotaxis; collagen; fibroblasts; fibronectins; gel electrophoresis; granuloma; helminthic antigen; human tissue; immunofluorescence technique; laboratory mouse; lymphokines; macrophage; macrophage activating factor; monokines; parasitic liver disorder; radiotracer; schistosomiasis; tissue /cell culture

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.

该提案描述了研究的研究 理解细胞和分子网络的长期目标 参与调节纤维化，使慢性炎症复杂化。 这样的 知识可能建议预防药理策略 一般疾病中的病理纤维化。 我们将利用小鼠模型曼森感染的模型血吸虫感染。 在 努力评估如何在 体内分泌刺激成纤维细胞的分子（迁移， 扩散和分泌基质蛋白）我们将确定鼠 细胞杂交瘤来源的巨噬细胞激活因子（S）[MAF]可以刺激 体外静止的巨噬细胞分泌纤维化物质。 我们将 测试这种MAF活性在1）肉芽肿培养中的存在 上清液2）来自解离肉芽肿细胞悬浮液的上清液 富含T淋巴细胞和3）敏化脾细胞的上清液 用鸡蛋抗原在体外触发。 我们还将测试 肉芽肿T细胞以直接成纤维细胞刺激性分泌淋巴动物 活动。 生物活性的生化表征 将执行物质。 还将特别关注 细胞因子刺激纤连蛋白分泌的能力 成纤维细胞。 分泌的一些生物学后果 纤连蛋白（巨噬细胞激活和成纤维细胞和单核细胞/巨噬细胞 将研究趋化性）。