Accelerated generation of CD14+ monocyte-lineage cells from the bone marrow of rheumatoid arthritis patients

Arthritis Rheum. 1996 May;39(5):836-43. doi: 10.1002/art.1780390517.

Abstract

Objective: To examine the capacity of bone marrow progenitor cells to generate CD14+ cells, in order to assess the role of bone marrow in the pathogenesis of rheumatoid arthritis (RA).

Methods: CD14- cells purified from bone marrow specimens of 11 patients with active RA and 8 control patients (osteoarthritis or trauma) were cultured in the presence or absence of granulocyte-macrophage colony-stimulating factor (GM-CSF; 100 pg/ml). After incubation for various lengths of time, the cells were analyzed by flow cytometry for expression of CD14 and HLA-DR.

Results: The spontaneous generation of CD14+ cells from bone marrow CD14- progenitor cells was accelerated in RA patients compared with control patients. Moreover, the expression of HLA-DR on the bone marrow-derived CD14+ cells was also accelerated in RA patients compared with controls. GM-CSF significantly enhanced the generation of CD14+ cells, as well as the expression of HLA-DR, on CD14+ cells of control patients, but not those of RA patients. GM-CSF levels in the culture supernatants of bone marrow CD14- cells were not significantly different between RA patients and control patients (undetectable in most cases).

Conclusion: These observations strongly support the hypothesis that the accelerated generation of CD14+ cells from bone marrow progenitor cells and the accelerated maturation of such CD14+ cells into HLA-DR+ cells play an important role in the pathogenesis of RA. Moreover, the data suggest a functional alteration of RA bone marrow CD14- cells in their responsiveness to GM-CSF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology*
  • Bone Marrow / immunology*
  • Bone Marrow / pathology
  • Cell Division
  • Cell Line
  • Female
  • HLA-DR Antigens / analysis
  • Humans
  • Lipopolysaccharide Receptors / analysis*
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Monocytes / pathology*
  • Stem Cells / immunology

Substances

  • HLA-DR Antigens
  • Lipopolysaccharide Receptors