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Macrophage inflammatory protein-1 alpha. A novel chemotactic cytokine for macrophages in rheumatoid arthritis

A E Koch1, S L Kunkel, L A Harlow

  • 1Department of Medicine, Northwestern University Medical School, Chicago, Illinois.

The Journal of Clinical Investigation
|March 1, 1994
PubMed

Insights

Macrophage inflammatory protein-1 alpha (MIP-1 alpha) is elevated in rheumatoid arthritis (RA) synovial fluid, attracting macrophages to inflamed joints. This study confirms MIP-1 alpha

Area of Science:

  • Immunology
  • Rheumatology
  • Cell Biology

Background:

  • Human macrophages play a critical role in cytokine elaboration in rheumatoid arthritis (RA).
  • Macrophage inflammatory protein-1 alpha (MIP-1 alpha) is a recently described cytokine with chemotactic activity for macrophages and neutrophils.

Purpose of the Study:

  • To investigate the production and role of MIP-1 alpha in rheumatoid arthritis.
  • To determine if MIP-1 alpha contributes to the recruitment of macrophages in synovial inflammation.

Main Methods:

  • Quantification of MIP-1 alpha in serum, synovial fluid (SF), and synovial tissue (ST) from 63 arthritic patients using immunoassays.
  • Assessment of MIP-1 alpha's chemotactic activity on macrophages and neutrophils.
  • Analysis of MIP-1 alpha production by mononuclear cells and synovial tissue fibroblasts/macrophages.
  • Immunohistochemical analysis of MIP-1 alpha expression in synovial tissue.

Main Results:

  • MIP-1 alpha levels were significantly higher in RA SF compared to other arthritis forms, osteoarthritis, and peripheral blood.
  • Anti-MIP-1 alpha antibodies neutralized a significant portion of the chemotactic activity for macrophages in RA SF.
  • MIP-1 alpha was produced by mononuclear cells and constitutively expressed by macrophages in RA synovial tissue.
  • Immunohistochemistry revealed MIP-1 alpha+ cells in RA synovial tissue were predominantly macrophages and lining cells.

Conclusions:

  • MIP-1 alpha is significantly elevated in rheumatoid arthritis synovial fluid.
  • MIP-1 alpha contributes to the chemotaxis of macrophages in RA.
  • MIP-1 alpha plays a role in the selective recruitment of macrophages during synovial inflammation in RA.

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