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.
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 RApatients compared with control patients. Moreover, the expression of HLA-DR on the bone marrow-derived CD14+ cells was also accelerated in RApatients 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 RApatients. GM-CSF levels in the culture supernatants of bone marrow CD14- cells were not significantly different between RApatients 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.
Authors: Charles E Breeze; Dirk S Paul; Jenny van Dongen; Lee M Butcher; John C Ambrose; James E Barrett; Robert Lowe; Vardhman K Rakyan; Valentina Iotchkova; Mattia Frontini; Kate Downes; Willem H Ouwehand; Jonathan Laperle; Pierre-Étienne Jacques; Guillaume Bourque; Anke K Bergmann; Reiner Siebert; Edo Vellenga; Sadia Saeed; Filomena Matarese; Joost H A Martens; Hendrik G Stunnenberg; Andrew E Teschendorff; Javier Herrero; Ewan Birney; Ian Dunham; Stephan Beck Journal: Cell Rep Date: 2016-11-15 Impact factor: 9.423
Authors: Yannick van Sleen; Qi Wang; Kornelis S M van der Geest; Johanna Westra; Wayel H Abdulahad; Peter Heeringa; Annemieke M H Boots; Elisabeth Brouwer Journal: Sci Rep Date: 2017-07-26 Impact factor: 4.379
Authors: Johanna Westra; Berber Doornbos-van der Meer; Peter de Boer; Miek A van Leeuwen; Martin H van Rijswijk; Pieter C Limburg Journal: Arthritis Res Ther Date: 2004-06-21 Impact factor: 5.156