Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis

Alisa E. Koch*, Steven L. Kunkel, Lisa A. Harlow, Bruce Johnson, Holly L. Evanoff, G. Kenneth Haines, Marie D. Burdick, Richard M. Pope, Robert M. Strieter

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

553 Scopus citations

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. MCP1 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-1β, tumor necrosis factor-alpha (TNF-α), 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.

Original languageEnglish (US)
Pages (from-to)772-779
Number of pages8
JournalJournal of Clinical Investigation
Volume90
Issue number3
DOIs
StatePublished - 1992

Keywords

  • Chemotaxis
  • Cytokine
  • Mononuclear phagocytes
  • Synovial fluid
  • Synovium

ASJC Scopus subject areas

  • Medicine(all)

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