Functional folate receptor beta-expressing macrophages in osteoarthritis synovium and their M1/M2 expression profiles

Objective: The distribution of folate receptor (FR)-beta+ 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. Method: The phenotypes and fluorescein isothiocyanate (FITC)-folate uptake of FR-beta+ synovial macrophages were analysed by flow cytometry. The distribution of FR-beta+ macrophages in OA and RA synovial tissues was examined by immunofluorescent microscopy. Tumour necrosis factor (TNF)-alpha, inducible nitric oxide synthase (iNOS), interleukin (IL)-10, and transforming growth factor (TGF)-beta expression in FR-beta+ macrophages was detected by doubleimmunostaining in both OA and RA synovial tissues. Results: FR-beta+ macrophages were predominantly present in the synovial lining layer in OA patients. The proportion of CD163-FR-beta+ cells in synovial mononuclear cells (MNCs) was increased in OA compared to RA synovial tissues. FR-beta(high) macrophages from OA synovial tissues represented the majority of folic acid-binding cells. Although FR-beta+ 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-beta+ synovial macrophages were different between OA and RA synovial tissues. Thus, the findings underscore that the M1/M2 paradigm using surface markers FR-beta and CD163 is an oversimplification of macrophage subsets. Functional FR-beta present on OA synovial macrophages provides a potential tool for the diagnosis and treatment of OA.