FIBROBLAST STIMULATION IN SCHISTOSOMIASIS

肝纤维化是#年严重发病率和死亡率的主要原因。 曼氏血吸虫病。这个项目的长期目标是 明确肝纤维化的分子和细胞基础 血吸虫病，可以有实际应用的知识，可以 与其他各种纤维化疾病有关(如肺 结节病和系统性硬化症)。 肝脏虫卵肉芽肿产生的纤维化细胞因子(包括 一种新的肝素结合素--成纤维细胞刺激因子-1[L 淋巴因子)显然在肝纤维化形成中起重要作用； 对这一生产或影响的下调可能会有好处 后果。L口蹄疫将通过口蹄疫L基因的分子克隆进行分析 并在COS细胞中表达。L的氨基酸序列将是 从cDNA的核苷酸序列衍生并与多肽进行比较 在天然序列中直接确定的序列-L和其他序列 数据库中的蛋白质。纯化的重组fsf-L将用于 间充质细胞表面Fsf-L受体的检测及单抗的制备 和多克隆抗体，用于FSF-L的免疫分析。这 实验和fsf-L cDNA探针将被用来研究 FSF-1在慢性血吸虫病中的免疫调节作用受感染的小鼠会 输注慢性感染小鼠的脾细胞亚群 并选择抗细胞因子抗体和肝脏虫卵肉芽肿 将对受者在8周内发生的疾病进行分析-L 制作。

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.