In long-established rheumatoid nodules, monocytes continue to be recruited and to migrate from the outer vascular zone toward the palisade and central necrotic area. Maturation of these cells is shown to take place during tissue migration. We found that the great majority of palisade cells express exclusive mononuclear phagocyte phenotypes. Among this mononuclear phagocyte population are many cells that bear the receptor for iC3b (CR3), but few that bear the receptor for C3b (CR1). HLA-D region molecule expression is intense and widespread.The pathogenesis of the subcutaneous rheumatoid nodule is not understood. These nodules develop in about 20% of patients with rheumatoid arthritis (RA) and are associated with circulating rheumatoid factors and with more severe erosive disease (1). Such lesions are necrotizing granulomas with a characteristic orderly arrangement of cells.Although the majority of patients with RA never develop nodules, lesions that appear to be identical to rheumatoid nodules are sometimes seen in otherwise healthy people, children in particular, in the absence of joint involvement (2). The relationship between the intimal cell hyperplasia and chronic inflammatory cell infiltrate, which characterize the synovium of joints affected with RA, and the granulomatous nodule is unclear.The general histologic characteristics of the subcutaneous nodule have been accepted for some 50 years (3), but the nature of the cellular infiltrate itself has been open to debate. The radially arranged palisade of cells which surrounds the necrotic center has been said to consist of fibroblasts (4), macrophage-like cells (3, or both of these cell forms (6). The controversy has not been settled by recent studies in which monoclonal antibodies were used. Hedfors et a1 (7) found that the palisading cells expressed HLA-D region antigens and the macrophage phenotype OKM 1 (8); moreover, these cells expressed the T helper cell markers Leu-3a and OKT4, which as others have found, are also expressed by macrophages (9). Thus, none of these markers are expressed exclusively by macrophages. Duke et a1 (10) confirmed that the palisade cells were HLA-D region-positive and that a further macrophage phenotype, FMC-17, was frequently expressed. However, the monoclonal antibody FMC-17 also shows weak reactivity with cells other than mononuclear phagocytes (1 1).We have extended these earlier observations by studying the distribution of cells that bear epitopes which not only specifically identify mononuclear phagocytes, but also reflect their maturational stage. In addition, we have demonstrated that the complement receptor for iC3b, but not that for C3b, is expressed by these cells.

The mononuclear phagocyte infiltrate which occupies the gout tophus has been compared with that of the subcutaneous rheumatoid nodule. In the gout tophus, macrophage migration appears to be at a relatively low level and effectively terminates once these cells have been recruited into the corona. In the nodule the evidence suggests that both macrophage and granulocyte populations continuously migrate towards, and are progressively incorporated into, the necrotic centres. These observations indicate that chemotactic activity in rheumatoid nodules is at a higher level than in gout tophi, or that the rheumatoid mononuclear phagocyte is more responsive to such stimuli.