IMMUNE MEDIATED ALTERATIONS IN CONNECTIVE TISSUE

硬皮病的特征是胶原过度堆积和 皮肤和内脏器官中的其他基质成分。成纤维细胞 从硬皮病患者皮肤分离合成增多 大量的胶原蛋白，这是一种在体外可繁殖的特性。我们之前 证明正常成纤维细胞是表型异质性的。 他们的代谢活动。假设正常的克隆选择 高胶原合成成纤维细胞的发生是一种致病因素 硬皮病的发病机制将作为工作模型来研究 这是这种疾病中代谢活动异常的基础。有选择性的 硬皮病成纤维细胞过度生长可能是由免疫产物介导的 渗入硬皮病皮肤的细胞和/或生长因子等 结缔组织环境中的介体。免疫的渗入 细胞，以及随后的介质释放，可能部分地通过特定的 淋巴细胞和成纤维细胞上的黏附配体。 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他调节身体的介质 试图基于表面标记来区分克隆 成纤维细胞群。单克隆性硬皮病皮肤原位研究 区分克隆性成纤维细胞群体的抗体将是 使用的组成群体，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。 类似的研究将对克隆的成纤维细胞群体进行 硬皮病和正常皮肤。最后，为了研究可能的基础， 免疫细胞在硬皮病皮肤中的定位，我们将检查 硬皮病淋巴细胞和/或成纤维细胞粘附性增加 属性以及它们是否表现出不正常的粘附量 配体LFA-1和ICAM。

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.