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 α

Bent W. Deleuran, Cong‐Qiu ‐Q Chu, Max Field, Fionula M. Brennan, Tracey Mitchell, Marc Feldmann, Ravinder N. Maini

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194 Scopus citations

Abstract

Objective. We have previously described the location of tumor necrosis factor α (TNFα)–producing cells in synovial tissue and cartilage–pannus junction in rheumatoid arthritis (RA). To further understand the local actions of TNFα, 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 TNFα‐containing cells, and some TNFα‐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 TNFα in this tissue. This study further supports the hypothesis that TNFα plays a major role in the pathogenesis of RA.

Original languageEnglish (US)
Pages (from-to)1170-1178
Number of pages9
JournalArthritis & Rheumatism
Volume35
Issue number10
DOIs
StatePublished - Oct 1992

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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