FIBROBLAST STIMULATION IN SCHISTOSOMIASIS

肝纤维化是肝硬化患者严重发病和死亡的主要原因， 曼氏血吸虫病 该项目的长期目标是 明确肝纤维化的分子和细胞基础 血吸虫病，知识，可以有实际应用， 与多种其他纤维化疾病（如肺纤维化）相关 结节病和系统性硬化症）。 肝虫卵肉芽肿产生的纤维化细胞因子（包括 成纤维细胞刺激因子-1 淋巴因子）在肝纤维化发生中起重要作用; 这种生产或影响的下调可能会有益于 后果 FsF-1cDNA的分子克隆将对FsF-1cDNA进行分析 并在COS细胞中表达。 FSF-1的氨基酸序列将是 来自cDNA的核苷酸序列，并与肽进行比较 在天然FSF-1中直接确定的序列和用于其它FSF-1的序列。 数据库中的蛋白质。 纯化的重组FsF-1将用于 评估间充质细胞上的FSF-1受体，并制备单克隆抗体， 和用于FsF-1免疫测定的多克隆抗体。 这 将使用FsF-1 cDNA探针来研究FsF-1基因的表达。 FsF-1在慢性血吸虫病中免疫调节作用 受感染的老鼠会 输注来自慢性感染小鼠的脾细胞亚群 选择性抗细胞因子抗体和肝虫卵肉芽肿 将对受体中8周时产生的FSF-1进行分析 生产

Liver fibrosis is the major cause of serious morbidity and mortality in schistosomiasis mansoni. The long-range goal of this project is to define the molecular and cellular basis of hepatic fibrosis in schistosomiasis, knowledge that can have practical applications and could be relevant to a variety of other fibrotic diseases (such as pulmonary sarcoid and systemic sclerosis). Fibrogenic cytokines produced by hepatic egg granulomas (including fibroblast stimulating factor-1 [FsF-l], a novel heparin-binding lymphokine) apparently play an important role in hepatic fibrogenesis; down-regulation of this production or effect may have salutary consequences. FsF-l will be analysed by molecular cloning of FsF-l cDNA and expression in COS cells. Amino acid sequence of FsF-l will be derived from the nucleotide sequence of cDNA and compared to peptide sequences directly determined in natural FsF-l and to sequences for other proteins in a databank. Purified recombinant FsF-l will be used to assess FsF-l receptors on mesenchymal cells, and to prepare monoclonal and polyclonal antibodies for use in an immunoassay for FsF-l. This assay and FsF-l cDNA probes will be used to investigate aspects of the immunoregulation of FsF-1 in chronic schistosomiasis. Infected mice will be infused with splenocyte subpopulations from chronically-infected mice and with selected anticytokine antibody and the hepatic egg granulomas that develop at 8 weeks in the recipients will be analysed for FsF-l production.