Ivarsson M, McWhirter A, Black C M, Rubin K
Department of Medical and Physiological Chemistry, University of Uppsala, Sweden.
J Invest Dermatol. 1993 Aug;101(2):216-21. doi: 10.1111/1523-1747.ep12364810.
We explored the hypothesis that dermal fibroblasts isolated from patients suffering from systemic sclerosis are disturbed in their ability to interact functionally with native collagen fibers. Additionally, we investigated the expression of one collagen-binding integrin matrix receptor, alpha 1 beta 1 on those cells. Two populations of primary dermal fibroblasts were established, one from patients with systemic sclerosis and one from normal subjects. When cultured for 24 h in free-floating collagen gels, both types of fibroblasts down-regulated the cellular content of collagen pro-alpha 1(I) messenger ribonucleic acid, the systemic sclerosis fibroblasts less markedly than the normals. In normal, but not in systemic sclerosis fibroblasts, the kinetics of collagen gel contraction were directly proportional to the extent of the down-regulation. Fetal bovine serum stimulated collagen gel contraction in both populations. When grown in collagen gels in the presence of fetal bovine serum, no difference between systemic sclerosis and normal fibroblasts in capacity to down-regulate pro-alpha 1(I) was observed. Collagen-binding beta 1 integrins mediate the functional interactions between fibroblasts and the collagen fibers. To assess the cell surface expression of collagen-binding beta 1 integrins on fibroblasts, we labeled cells with 125I and subjected Triton X-100 extracts from them to immunoprecipitation with anti-beta 1 integrin immunoglobulin G. Among the systemic sclerosis fibroblasts, a larger number of isolates expressed low amount of alpha 1 beta 1 than did the fibroblasts isolated from normal individuals. Our data are compatible with the hypothesis that systemic sclerosis fibroblasts have a disturbed interaction with collagen fibers; this disturbance may in part be the result of an aberrant expression of collagen-binding beta 1 integrins.
我们探究了一个假说，即从系统性硬化症患者分离出的真皮成纤维细胞在与天然胶原纤维进行功能相互作用的能力方面存在紊乱。此外，我们研究了一种胶原结合整合素基质受体α1β1在这些细胞上的表达情况。建立了两类原代真皮成纤维细胞群体，一类来自系统性硬化症患者，另一类来自正常受试者。当在自由漂浮的胶原凝胶中培养24小时时，两种类型的成纤维细胞均下调了胶原原α1（I）信使核糖核酸的细胞含量，系统性硬化症成纤维细胞下调的程度不如正常成纤维细胞明显。在正常成纤维细胞而非系统性硬化症成纤维细胞中，胶原凝胶收缩的动力学与下调程度直接成正比。胎牛血清刺激了两类细胞群体的胶原凝胶收缩。当在胎牛血清存在的情况下于胶原凝胶中生长时，未观察到系统性硬化症成纤维细胞与正常成纤维细胞在下调原α1（I）能力上的差异。胶原结合β1整合素介导成纤维细胞与胶原纤维之间的功能相互作用。为评估成纤维细胞上胶原结合β1整合素的细胞表面表达情况，我们用125I标记细胞，并将来自这些细胞的Triton X - 100提取物用抗β1整合素免疫球蛋白G进行免疫沉淀。在系统性硬化症成纤维细胞中，与从正常个体分离出的成纤维细胞相比，有更多分离株表达低水平的α1β1。我们的数据与系统性硬化症成纤维细胞与胶原纤维相互作用紊乱这一假说相符；这种紊乱可能部分是胶原结合β1整合素异常表达的结果。
