Pirilä L, Aho H, Roivainen A, Konttinen Y T, Pelliniemi L J, Heino J
MediCity Research Laboratory, Medical Biochemistry, University of Turku, Finland.
J Rheumatol. 2001 Mar;28(3):478-84.
In rheumatoid arthritis (RA) the synovial lining is responsible for cartilage destruction. Laminin is one of the major matrix molecules surrounding the lining cells. We investigated the laminin adhesion mechanism of synovial lining cells by analyzing the presence of its receptor, alpha6beta1 integrin, on type A and type B synoviocytes.
The alpha6 integrin subunit and a macrophage marker were simultaneously localized by immunohistochemistry in 29 RA derived, 6 osteoarthritis derived, and 2 healthy synovial samples by light and electron microscopy. We also used enzyme treatments to release cells from synovial tissue samples and localized the same antigens on adherent cells.
The alpha6beta1 integrin positive cells were localized in basal areas of the lining layer and many of them were negative for the macrophage markers. By immunolabeling electron microscopy the alpha6 integrin positive cells were confirmed to represent the fibroblast-like type B cells. Further, in freshly isolated synoviocyte cultures the type B cells were positive for alpha6 integrin, whereas all other cell types were negative for this laminin receptor.
Integrin alpha6beta1 is known to be a laminin receptor of endothelial cells, adipocytes, and macrophages, not usually expressed on fibroblasts. However, in synovial lining layer it is expressed on fibroblastic type B cells, but the macrophage population is negative. The unique characteristics of synovial lining cells distinguish them from other connective tissue cells and must be taken into account in all considerations of the pathogenic mechanisms of rheumatoid disease.
在类风湿关节炎(RA)中,滑膜衬里负责软骨破坏。层粘连蛋白是围绕衬里细胞的主要基质分子之一。我们通过分析A、B型滑膜细胞上其受体α6β1整合素的存在情况,研究了滑膜衬里细胞的层粘连蛋白黏附机制。
通过免疫组织化学,利用光镜和电镜对29份类风湿关节炎来源、6份骨关节炎来源以及2份健康滑膜样本中的α6整合素亚基和巨噬细胞标志物进行同步定位。我们还采用酶处理从滑膜组织样本中释放细胞,并对贴壁细胞上的相同抗原进行定位。
α6β1整合素阳性细胞定位于衬里层的基底区域,其中许多细胞的巨噬细胞标志物呈阴性。通过免疫标记电子显微镜证实,α6整合素阳性细胞代表成纤维细胞样B型细胞。此外,在新鲜分离的滑膜细胞培养物中,B型细胞的α6整合素呈阳性,而所有其他细胞类型的这种层粘连蛋白受体均为阴性。
已知整合素α6β1是内皮细胞、脂肪细胞和巨噬细胞的层粘连蛋白受体,通常不在成纤维细胞上表达。然而,在滑膜衬里层中,它在成纤维细胞样B型细胞上表达,但巨噬细胞群体呈阴性。滑膜衬里细胞的独特特征使其有别于其他结缔组织细胞,在类风湿病发病机制的所有考量中都必须予以考虑。