FIBROBLAST STIMULATION IN SCHISTOSOMIASIS

血吸虫病中的成纤维细胞刺激

• 批准号: 3127301
• 负责人: DAVID J WYLER
• 金额: $ 19.77万
• 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 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3127301
• 关键词: Schistosoma mansoni; antiantibody; athymic mouse; autoradiography; enzyme linked immunosorbent assay; fibroblast growth factor; fibrosis; granuloma; growth factor receptors; helminthic antigen; human tissue; immunofluorescence technique; laboratory mouse; laboratory rat; lymphokines; molecular cloning; molecular pathology; monoclonal antibody; northern blottings; nucleic acid probes; nucleic acid sequence; parasitic liver disorder; protein purification; protein sequence; radionuclides; radiotracer; schistosomiasis; tissue /cell culture; transfection

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.

肝纤维化是严重发病率和死亡率的主要原因 血吸虫病Mansoni。 这个项目的远程目标是 定义肝纤维化的分子和细胞基础 血吸虫病，可以具有实际应用的知识，并且可以 与各种其他纤维化疾病有关（例如肺部 结节和全身性硬化）。 由肝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 [FSF-L]，一种新型的肝素结合 淋巴动物显然在肝纤维发生中起重要作用； 该生产或效果的下调可能会有益 结果。 FSF-L将通过FSF-L cDNA的分子克隆来分析 和COS细胞中的表达。 FSF-L的氨基酸序列将是 源自cDNA的核苷酸序列并与肽进行比较 在天然FSF-L中直接确定的序列和其他 数据库中的蛋白质。 纯化的重组FSF-L将用于 评估间充质细胞上的FSF-L受体，并制备单克隆 用于用于FSF-L的免疫测定中的多克隆抗体。 这 测定和FSF-L cDNA探针将用于研究 FSF-1在慢性血吸虫病中的免疫调节。 感染的小鼠会 注入慢性感染小鼠的脾细胞亚群 并具有选定的抗细节抗体和肝卵肉芽肿 将分析FSF-L的第8周在接受者中发展的 生产。