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

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.