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


CONCLUSIONS
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.
Hirohata
S
S
Teikyo University School of Medicine, Tokyo, Japan.
Yanagida
T
T
Itoh
K
K
Nakamura
H
H
Yoshino
S
S
Tomita
T
T
Ochi
T
T
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology*; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology; D002455:Cell Division; D002460:Cell Line; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000473:pathology*; D013234:Stem Cells / Q000276:immunology
D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors