IMMUNE MEDIATED ALTERATIONS IN CONNECTIVE TISSUE

结缔组织中免疫介导的改变

• 批准号: 2078826
• 负责人: JOSEPH H KORN
• 金额: $ 21.87万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-10-01 至 1995-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2078826
• 关键词: cell adhesion molecules; cellular immunity; clone cells; collagen; collagenase; connective tissue cells; cytogenetics; cytokine; epidermal growth factor; fibroblasts; gene expression; in situ hybridization; laboratory mouse; lymphocyte; membrane activity; monoclonal antibody; monocyte; rheumatoid arthritis; scleroderma; surface antigens

Scleroderma is characterized by excessive accumulation of collagen and other matrix components in the skin and visceral organs. Fibroblasts isolated from the skin of patients with scleroderma synthesize increased amounts of collagen, a property that is propagable in vitro. We previously demonstrated that normal fibroblast are phenotypically heterogeneous in their metabolic activity. The hypothesis that clonal selection of normally occuring, high collagen synthesizing fibroblasts, is a pathogenetic mechanism in scleroderma will be used as a working model to examine the basis for abnormal metabolic activity in this disorder. Selective overgrowth of scleroderma fibroblasts may be mediated by products of immune cells, which infiltrate scleroderma skin, and/or growth factors and other mediators in the connective tissue environment. The infiltration of immune cells, and subsequent mediator release, may be mediated in part by specific adhesion ligands on lymphocytes and fibroblasts. We will determine whether scleroderma fibroblasts have abnormal sensitivity to immune cell derived cytokines and other mediators which regulate bodies in an attempt to distinguish, based on surface markers, among clonal fibroblast populations. In situ studies in scleroderma skin, monoclonal antibodies which distinguish among clonal fibroblast populations will be used constituent population, i.e. clonal restriction. These studies will be combined with analysis of collagen production by in situ hybridization. Similar studies will be performed with fibroblast populations cloned from scleroderma and normal skin. Finally, to examine a possible basis for immune cell localization in scleroderma skin, we will examine whether scleroderma lymphocytes and/or fibroblasts show increased adhesive properties and whether they express abnormal amounts of the adhesion ligands LFA-1 and ICAM.

硬皮病的特征在于胶原蛋白的过度积累， 皮肤和内脏器官中的其他基质成分。 成纤维 从硬皮病患者的皮肤中分离出来， 大量的胶原蛋白，这是一种可以在体外繁殖的特性。 我们之前 表明正常成纤维细胞在表型上是异质的， 他们的代谢活动。 克隆选择的假设是， 高胶原合成的成纤维细胞，是一种致病因素， 机制硬皮病将被用作一个工作模型，以检查 这种疾病中代谢活动异常的基础。 选择性 硬皮病成纤维细胞的过度生长可能是由免疫反应产物介导的。 细胞和/或生长因子以及其它 结缔组织环境中的介质。 免疫浸润 细胞，以及随后的介质释放，可以部分地由特异性 淋巴细胞和成纤维细胞上的粘附配体。 我们将确定硬皮病成纤维细胞是否具有异常敏感性 免疫细胞衍生的细胞因子和其它调节机体的介质 在尝试基于表面标记区分克隆 成纤维细胞群。 硬皮病皮肤的原位研究，单克隆 区分克隆成纤维细胞群体的抗体将被 使用组成群体，即克隆限制。 这些研究将 结合原位杂交分析胶原蛋白的产生。 类似的研究将用从人成纤维细胞克隆的成纤维细胞群进行。 硬皮病和正常皮肤。 最后，研究一个可能的基础， 免疫细胞定位在硬皮病皮肤，我们将研究是否 硬皮病淋巴细胞和/或成纤维细胞表现出增加的粘附性， 性能以及它们是否表现出异常的粘附量 配体LFA-1和ICAM。