PMID- 1522232 OWN - NLM STAT- MEDLINE DCOM- 19921013 LR - 20220227 IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 90 IP - 3 DP - 1992 Sep TI - Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis. PG - 772-9 AB - 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 less than 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 less than 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. FAU - Koch, A E AU - Koch AE AD - Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611. FAU - Kunkel, S L AU - Kunkel SL FAU - Harlow, L A AU - Harlow LA FAU - Johnson, B AU - Johnson B FAU - Evanoff, H L AU - Evanoff HL FAU - Haines, G K AU - Haines GK FAU - Burdick, M D AU - Burdick MD FAU - Pope, R M AU - Pope RM FAU - Strieter, R M AU - Strieter RM LA - eng GR - AR30692/AR/NIAMS NIH HHS/United States GR - AR41492/AR/NIAMS NIH HHS/United States GR - HL-02401/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Chemokine CCL2) RN - 0 (Chemotactic Factors) RN - 0 (Interleukin-8) RN - 0 (RNA, Messenger) SB - IM MH - Arthritis, Rheumatoid/*metabolism MH - Base Sequence MH - Chemokine CCL2 MH - Chemotactic Factors/analysis/*biosynthesis/genetics MH - Fibroblasts/metabolism MH - Humans MH - Immunohistochemistry MH - Interleukin-8/analysis MH - Macrophages/metabolism MH - Molecular Sequence Data MH - RNA, Messenger/analysis MH - Synovial Fluid/metabolism PMC - PMC329929 EDAT- 1992/09/01 00:00 MHDA- 1992/09/01 00:01 PMCR- 1992/09/01 CRDT- 1992/09/01 00:00 PHST- 1992/09/01 00:00 [pubmed] PHST- 1992/09/01 00:01 [medline] PHST- 1992/09/01 00:00 [entrez] PHST- 1992/09/01 00:00 [pmc-release] AID - 10.1172/JCI115950 [doi] PST - ppublish SO - J Clin Invest. 1992 Sep;90(3):772-9. doi: 10.1172/JCI115950.