Johnson B A, Haines G K, Harlow L A, Koch A E
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611.
Arthritis Rheum. 1993 Feb;36(2):137-46. doi: 10.1002/art.1780360203.
We have previously shown that E-selectin is expressed on endothelium in rheumatoid arthritis (RA) synovial tissues, and hence may be important in recruitment of leukocytes into the inflamed joint. In the present study, we determined whether other cellular adhesion molecules, including selectins and members of the integrin and immunoglobulin supergene families, are expressed in frozen synovium.
We employed immunohistochemical staining to determine the distribution of CD31 (PECAM), CD44 (hyaluronate receptor), CD62 (P-selectin), Leu-8 (L-selectin), and the integrin subunits alpha 5 (VLA-5), alpha 6 (VLA-6), beta 1 (VLA 1-6), and beta 3 (vitro-nectin receptor), in synovial tissue from 9 RA and 9 osteoarthritis (OA) patients, and from 3 normal (NL) subjects.
P-selectin was expressed on vascular endothelium in all synovial tissues examined. L-selectin and alpha 5-integrin, while expressed on a variety of cell types, were not differentially expressed on RA synovial tissues. Integrin subunits alpha 6 and beta 1 were down-regulated on some RA synovial tissue components. In contrast, CD31 was expressed to a greater extent on RA than on OA lining cells and macrophages (P < 0.05). CD44 was expressed to a greater extent on RA or OA macrophages, lining cells, and fibroblasts compared with NL (P < 0.05). Integrin subunit beta 3 was strongly expressed on RA synovial blood vessels compared with NL (P < 0.05).
The expression of integrins VLA 1-6, and selectins P and L is not up-regulated in RA synovial tissues. CD31 and CD44 are up-regulated on RA macrophages and lining cells, CD44 on RA fibroblasts, and beta 3-integrin on RA blood vessels. The up-regulation of CD31, CD44, and beta 3-integrin in RA synovial tissues may help tip the balance of adhesive interactions toward passage and retention of leukocytes in the inflamed joint.
我们之前已经表明,E-选择素在类风湿关节炎(RA)滑膜组织的内皮细胞上表达,因此在白细胞募集到炎症关节中可能起重要作用。在本研究中,我们确定了包括选择素、整合素家族成员和免疫球蛋白超基因家族成员在内的其他细胞粘附分子是否在冷冻滑膜中表达。
我们采用免疫组织化学染色来确定9例RA患者、9例骨关节炎(OA)患者以及3例正常(NL)受试者的滑膜组织中CD31(血小板内皮细胞粘附分子)、CD44(透明质酸受体)、CD62(P-选择素)、Leu-8(L-选择素)以及整合素亚基α5(VLA-5)、α6(VLA-6)、β1(VLA 1-6)和β3(体外粘连蛋白受体)的分布。
在所检查的所有滑膜组织中,P-选择素在血管内皮细胞上表达。L-选择素和α5-整合素虽然在多种细胞类型上表达,但在RA滑膜组织中没有差异表达。整合素亚基α6和β1在一些RA滑膜组织成分上表达下调。相比之下,CD31在RA中的表达程度高于OA衬里细胞和巨噬细胞(P < 0.05)。与NL相比,CD44在RA或OA巨噬细胞、衬里细胞和成纤维细胞上的表达程度更高(P < 0.05)。与NL相比,整合素亚基β3在RA滑膜血管上强烈表达(P < 0.05)。
在RA滑膜组织中,整合素VLA 1-6以及选择素P和L的表达没有上调。CD�和CD44在RA巨噬细胞和衬里细胞上上调,CD44在RA成纤维细胞上上调,β3-整合素在RA血管上上调。RA滑膜组织中CD31、CD44和β3-整合素的上调可能有助于使粘附相互作用的平衡倾向于白细胞在炎症关节中的通过和滞留。