Date Published: November 17, 2009
Publisher: Public Library of Science
Author(s): Rogier M. Thurlings, Carla A. Wijbrandts, Roelof J. Bennink, Serge E. Dohmen, Carlijn Voermans, Diana Wouters, Elena S. Izmailova, Danielle M. Gerlag, Berthe L. F. van Eck-Smit, Paul P. Tak, Andrew Boswell. http://doi.org/10.1371/journal.pone.0007865
Abstract: Macrophages are principal drivers of synovial inflammation in rheumatoid arthritis (RA), a prototype immune-mediated inflammatory disease. Conceivably, synovial macrophages are continuously replaced by circulating monocytes in RA. Animal studies from the 1960s suggested that macrophage replacement by monocytes is a slow process in chronic inflammatory lesions. Translation of these data into the human condition has been hampered by the lack of available techniques to analyze monocyte migration in man.
Partial Text: Macrophages in the inflamed synovial tissue of rheumatoid arthritis (RA) patients play a central role in the sustenance of synovial inflammation and promotion of tissue destruction –. Conceivably they are continuously replaced by circulating monocytes . The dynamics of this replacement is a matter of controversy. Data on the effects of anti-rheumatic treatments suggest this might be a highly dynamic process –, while animal studies from the 1960s suggested it might occur at a slow rate –.
Eight RA patients (4 male and 4 female) were included into the study. The median age of the patients was 52 years (range 39 to 59 years) and the mean disease duration was 19 (range 10–38) years. Erosions were present in all patients. Two patients had nodular disease. Four patients were seropositive for IgM rheumatoid factor. The mean (±SD) disease activity score evaluated in 28 joints (DAS28) at screening was 5.8±0.8. All patients were treated with stable dosages of methotrexate.
In the present study we used a recently developed procedure, that visualizes the migratory behavior of monocytes , , to test the hypothesis that synovial inflammation in RA is maintained by influx of monocytes into the synovial compartment. The results suggest that while there is indeed a continuous influx of circulating monocytes into the synovial compartment, their numbers are small, indicating that only a relatively small fraction of synovial macrophages is replaced per day.