Chemoattractant Protein-1 in Rheumatoid Arthritis

Cells within the synovial tissuemay recruit mononuclear phagocytes into the synovial fluid and tissues ofarthritic patients.We investigated the production of the chemotactic cytokine monocyte chemoattractant protein-i (MCP-1) using sera, synovial fluid, synovial tissue, as well as macrophages and fibroblasts isolated from synovial tissues from 80 arthritic patients. MCP1 levels were significantly higher (P < 0.05) in synovial fluid from RA patients (mean 25.5±8.1 ng/ml ISEI) compared to synovial fluid from osteoarthritis (OA) patients (0.92±0.08), or from patients with other arthritides (2.9±1.5). MCP-1 levels in RA sera (8.44±2.33) were significantly greater than MCP-1 innormal sera (0.16±0.06).The quantities ofRA synovial fluid IL-8, which is chemotactic for neutrophils and lymphocytes, and MCP-1 were strongly positively correlated (P < 0.05). To examine the cellular source of MCP-1, RA synovial tissue macrophages and fibroblasts were isolated. Synovial tissue fibroblasts did not express MCP-1 mRNA, but could be induced to produce MCP-1 by stimulation with either IL-1#, tumor necrosis factor-alpha (TNF-a), or LPS. In contrast, unlike normal peripheral blood monocytes or alveolar macrophages, RA synovial tissue macrophages constitutively expressed MCP-1 mRNA and antigen. Immunohistochemical analysis of synovial tissue showed that a significantly greater percentage ofRA macrophages (50±8%) as compared to either OA macrophages (5±2) or normal macrophages (1±0.3) reacted with anti-MCP-1 antibodies. In addition, the synovial lining layer reacted with MCP-1 in both RA and OA synovial tissues. In contrast, only a minority of synovial fibroblasts (18±8%) fromRA synovium were positive for immunolocalization ofMCP-1. These results suggest that synovial production of MCP-1 may play an important role in the recruitment of mononuclear phagocytes during inflammation associated with RA and that synovial tissue macrophages are the dominant source of this cytokine. (J. Clin. Invest. 1992. 90:772-779.)