title: Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis.
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 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.
authors.affiliation: Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611.
authors.forename: A E
authors.initials: AE
authors.lastname: Koch
authors.forename: S L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: L A
authors.initials: LA
authors.lastname: Harlow
authors.forename: B
authors.initials: B
authors.lastname: Johnson
authors.forename: H L
authors.initials: HL
authors.lastname: Evanoff
authors.forename: G K
authors.initials: GK
authors.lastname: Haines
authors.forename: M D
authors.initials: MD
authors.lastname: Burdick
authors.forename: R M
authors.initials: RM
authors.lastname: Pope
authors.forename: R M
authors.initials: RM
authors.lastname: Strieter
mesh_terms: D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001483:Base Sequence; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000032:analysis; D008264:Macrophages / Q000378:metabolism; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D013582:Synovial Fluid / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016209:Interleukin-8; D012333:RNA, Messenger