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| ENHANCED PRODUCTION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN RHEUMATOID-ARTHRITIS |
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| Author(s): KOCH AE, KUNKEL SL, HARLOW LA, JOHNSON B, EVANOFF HL, HAINES GK, BURDICK MD, POPE RM, STRIETER RM |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 90 Issue: 3 Pages: 772-779 Published: SEP 1992 |
| Times Cited: 404 References: 52 |
| Abstract: Cells within the synovial tissue may recruit mononuclear phagocytes into the synovial fluid and tissues of arthritic patients. We investigated the production of the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1) using sera, synovial fluid, synovial tissue, as well as macrophages and fibroblasts isolated from synovial tissues from 80 arthritic patients. MCP-1 levels were significantly higher (P < 0.05) in synovial fluid from RA patients (mean 25.5+/-8.1 ng/ml [SE]) 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 in normal sera (0.16+/-0.06). The quantities of RA 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-beta, tumor necrosis factor-alpha (TNF-alpha), 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 of RA 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%) from RA synovium were positive for immunolocalization of MCP-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. |
| Document Type: Article |
| Language: English |
| Reprint Address: KOCH, AE (reprint author), NORTHWESTERN UNIV, SCH MED, DEPT MED, 303 E CHICAGO AVE, WARD BLDG 3-315, CHICAGO, IL 60611 USA |
Addresses:
1. NORTHWESTERN UNIV, SCH MED, DEPT PATHOL, CHICAGO, IL 60611 USA
2. LAKESIDE VET ADM MED CTR, CHICAGO, IL USA
3. UNIV MICHIGAN, MED CTR, ANN ARBOR, MI 48109 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: JN959 |
| ISSN: 0021-9738 |
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