Macrophage-like Cells of the Pannus Area in Rheumatoid Arthritic Joints

Abstract

Frozen sections of pannus tissue taken from the joints of patients with rheumatoid arthritis have been investigated using immunohistological methods to determine the distribution of subsets of macrophage-like cells in this area. A panel of monoclonal antibodies including reagents specific in normal tissue for interdigitating cells (RFD1), macrophages (RFD7), epithelioid cells, (RFD9), monocytes (UCHMI), and osteoclasts (263C), were used. Indirect immunoperoxidase and combination indirect immunofluorescence procedures revealed the phenotypes of macrophage-like cells in four histologically distinct areas of the tissue: the synovial lining layers, the deeper stroma, areas of perivascular infiltration, and the articular cartilage junction where degeneration was occurring. It was discovered that 80% of the lining cells and a majority of macrophage-like cells of the stroma, express the phenotype RFD1+ RFD7+ UCHMI+. Cells with a typical 'dendritic cell' phenotype (RFD1+ RFD7-) were only present in the perivascular infiltrates, while 'classic macrophages' (RFD7+ RFD1-) were the cells accumulating at the cartilage junction. No significant numbers of RFD9+ epithelioid cells were seen. 263C+ osteoclasts were present in small numbers distributed throughout the stroma but did not appear to be involved in areas of cartilage degradation. This cellular distribution in the pannus is compared with previous studies on the rheumatoid synovium proper. It is concluded that a distinct inflammatory reaction occurs in the pannus and that classic activated macrophages are the cells involved in cartilage degradation.

Synovial tissue macrophage populations and articular damage in rheumatoid arthritis

“…RFD7 expression was broadly similar to CD68 expression, but Ber-MAC3 expression was significantly lower than CD68 and RFD7 expression, suggesting that not all macrophages express this marker in rheumatoid synovium. These results extend the findings of earlier studies (33,43,44). The expression of some, but not other, macrophage markers by lining cells has been observed previously (33,36,37).…”

“…For this study, markers of activated/mature macrophages were chosen: EBMl 1 , which recognizes CD68, an antigen expressed primarily within lysosomes in tissue macrophages and monocytes but which may also be weakly expressed by type B synoviocytes in the lining layer (39,40); RFD7, which recognizes mature tissue macrophages (41); and Ber-MAC3, which recognizes activated monocytes and tissue macrophages (42). Synovial expression of Ber-MAC3 has not previously been described, but some authors have used macrophage markers comparable with EBMl 1 and RFD7 (33,43,44). These studies have been descriptive, and detailed quantification of macrophage numbers and their interrelationship has not been reported.…”

“…There is good evidence that many others also arise mainly from lining layer cells, both type A cells and type B synoviocytes (48-50). At the cartilage-pannus junction, where pannus leads to joint destruction, abundant macrophages and synovial fibroblasts are evident, and macrophage-derived cytokines have been demonstrated (43,51).…”

Changes in phenotypically distinct mucosal macrophage populations may be a prerequisite for the development of inflammatory bowel disease

“…As stated earlier, the normal colonic mucosal macrophage is phenotypically distinct from its counterparts elsewhere in the body in that it stains positively with both RFD1 and RFD7. Infiltration by D1/D7 doubles, however, is a feature of chronic inflammatory disorders affecting other tissues (Salisbury, Duke & Poulter, 1987;Noble, du Bois & Poulter, 1989;Spiteri, Clarke & Poulter, 1988). The small subset of DI/ D7 doubles isolated from normal human lung exhibits suppressor properties in functional studies (Spiteri & Poulter, 1991 al., 1989), and their participation within granulomas parallels that observed in sarcoidosis (Munro et al, 1987).…”

Reduced expression and proteolytic susceptibility of lubricin/superficial zone protein may explain early elevation in the coefficient of friction in the joints of rats with antigen‐induced arthritis

“…Classic features of RA include overgrowth of synovial tissue and formation of an aggressive cell mass (pannus) (1,2), initiated by infiltrating monocytes and macrophages (3). Destruction of articular cartilage and bone is attributed to a host of proteases, e.g., serine proteases, matrix metalloproteases, and cathepsins, secreted by the pannus tissue (4,5).…”