FIBROBLAST STIMULATION IN SCHISTOSOMIASIS

本提案描述了作为项目一部分的研究， 了解细胞和分子网络的长期目标 参与调节慢性炎症并发的纤维化。 等 知识可能会建议预防的药理学策略 病理性纤维化的一般疾病。 我们将利用曼氏血吸虫感染小鼠作为模型。 中 努力评估肝虫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 细胞杂交瘤衍生的巨噬细胞活化因子[MAF]可以刺激 静止的巨噬细胞在体外分泌纤维化物质。 我们将 在1）肉芽肿培养物中检测这种MAF活性的存在 2）来自解离的肉芽肿细胞悬浮液的上清液 富集T淋巴细胞，和3）致敏脾细胞的上清液 在体外用卵抗原触发。 我们还将测试 肉芽肿T细胞分泌淋巴因子与直接成纤维细胞刺激 活动 生物活性物质的生化表征 物质将被执行。 还将特别注意 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（巨噬细胞活化和成纤维细胞和单核细胞/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.