Functional folate receptor beta-expressing macrophages in osteoarthritis synovium and their M1/M2 expression profiles.
OBJECTIVE
The distribution of folate receptor (FR)-β+ macrophages and their M1/M2 expression profiles were examined in osteoarthritis (OA) synovial tissues, and compared to those in rheumatoid arthritis (RA) synovial tissues and CD163+ macrophages in both OA and RA synovial tissues.


METHODS
The phenotypes and fluorescein isothiocyanate (FITC)-folate uptake of FR-β+ synovial macrophages were analysed by flow cytometry. The distribution of FR-β+ macrophages in OA and RA synovial tissues was examined by immunofluorescent microscopy. Tumour necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), interleukin (IL)-10, and transforming growth factor (TGF)-β expression in FR-β+ macrophages was detected by double-immunostaining in both OA and RA synovial tissues.


RESULTS
FR-β+ macrophages were predominantly present in the synovial lining layer in OA patients. The proportion of CD163-FR-β+ cells in synovial mononuclear cells (MNCs) was increased in OA compared to RA synovial tissues. FR-β(high) macrophages from OA synovial tissues represented the majority of folic acid-binding cells. Although FR-β+ or CD163+ macrophages in the synovial tissues of OA and RA patients expressed a mixed pattern of M1 and M2 macrophage markers, there were more M2 markers expressing synovial macrophages in OA than in RA patients.


CONCLUSIONS
The distribution and M1/M2 expression profiles of FR-β+ synovial macrophages were different between OA and RA synovial tissues. Thus, the findings underscore that the M1/M2 paradigm using surface markers FR-β and CD163 is an oversimplification of macrophage subsets. Functional FR-β present on OA synovial macrophages provides a potential tool for the diagnosis and treatment of OA.
Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Y
Y
Tsuneyoshi
M
M
Tanaka
T
T
Nagai
N
N
Sunahara
T
T
Matsuda
T
T
Sonoda
K
K
Ijiri
S
S
Komiya
T
T
Matsuyama
D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D019645:Arthroplasty, Replacement, Knee; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D058976:Folate Receptor 2 / Q000378:metabolism*; D006801:Humans; D007719:Knee Joint / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020370:Osteoarthritis, Knee / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy; D010641:Phenotype; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
D018501:Antirheumatic Agents; D058976:Folate Receptor 2