LOCALIZATION OF TUMOR-NECROSIS-FACTOR RECEPTORS IN THE SYNOVIAL TISSUE AND CARTILAGE PANNUS JUNCTION IN PATIENTS WITH RHEUMATOID-ARTHRITIS - IMPLICATIONS FOR LOCAL ACTIONS OF TUMOR-NECROSIS-FACTOR-ALPHA
LOCALIZATION OF TUMOR-NECROSIS-FACTOR RECEPTORS IN THE SYNOVIAL TISSUE AND CARTILAGE PANNUS JUNCTION IN PATIENTS WITH RHEUMATOID-ARTHRITIS - IMPLICATIONS FOR LOCAL ACTIONS OF TUMOR-NECROSIS-FACTOR-ALPHA
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DOI：
10.1002/art.1780351009
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发表时间：
1992-10-01
影响因子：
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通讯作者：
MAINI, RN
中科院分区：
文献类型：
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作者：
DELEURAN, BW;CHU, CQ;MAINI, RN
目标。我们之前已经描述了类风湿性关节炎（RA）中滑膜组织和软骨-膜交界处产生肿瘤坏死因子α (TNFalpha)细胞的位置。为了进一步了解肿瘤坏死因子的局部作用，我们研究了肿瘤坏死因子受体（TNF- r）在ra患者相同区室细胞上的表达。采用碱性磷酸酶偶联小鼠抗碱性磷酸酶（apap）和单克隆抗体双免疫荧光染色技术检测p55和p75 TNF-R的表达。在RA滑膜中，p55 TNF-R和p75 TNF-R在高达90%的衬里层细胞中均可检测到，并且在膜较深层的细胞（包括血管内皮细胞）中也能检测到。淋巴样聚集体细胞均表达TNF-R，但主要表达p75受体。在软骨-肠膜交界处，大多数肠膜细胞，尤其是侵袭软骨细胞，同时表达p55和p75的TNF-R。序列切片和双免疫荧光染色显示，表达TNF-R的细胞位于含tnfalpha的细胞附近，部分含tnfalpha的细胞也表达TNF-R。在骨关节炎和正常滑膜组织中也检测到表达tnf - r的细胞，但数量较少，强度较低。这些结果提供了组织学证据，表明p55 TNF-R和p75 TNF-R在RA滑膜组织中由多种细胞类型表达，反映了该组织中广泛的细胞是TNFalpha的潜在靶点。本研究进一步支持了TNFalpha在RA发病机制中起主要作用的假设。
Objective. We have previously described the location of tumor necrosis factor alpha (TNFalpha)-producing cells in synovial tissue and cartilage-pannus junction in rheumatoid arthritis (RA). To further understand the local actions of TNFalpha, we investigated the expression of TNF receptors (TNF-R) on cells in the same compartments in patients with RA.Methods. The expression of both p55 TNF-R and p75 TNF-R was determined using alkaline phosphatase-conjugated mouse anti-alkaline phosphatase (APAAP) and double immunofluorescence staining techniques with monoclonal antibodies.Results. In RA synovial membrane, both p55 TNF-R and p75 TNF-R were detectable in up to 90% of the cells in the lining layer, and were demonstrated on cells in deeper layers of the membrane, including vascular endothelial cells. Cells in lymphoid aggregates expressed both TNF-R, but with a predominant expression of p75 receptor. At the cartilage-pannus junction, the majority of pannus cells, especially those invading cartilage, expressed both the p55 and the p75 TNF-R. Sequential section and double immunofluorescence staining showed that the TNF-R-expressing cells were in the vicinity of TNFalpha-containing cells, and some TNFalpha-containing cells also expressed TNF-R. TNF-R-expressing cells were also detected in osteoarthritic and normal synovial tissue, but in smaller numbers and at a lower intensity.Conclusion. These results provide histologic evidence that both p55 TNF-R and p75 TNF-R are expressed by a variety of cell types in RA synovial tissue, reflecting the fact that a wide range of cells are potential targets for TNFalpha in this tissue. This study further supports the hypothesis that TNFalpha plays a major role in the pathogenesis of RA.