Functional folate receptor beta-expressing macrophages in osteoarthritis synovium and their M1/M2 expression profiles
Functional folate receptor beta-expressing macrophages in osteoarthritis synovium and their M1/M2 expression profiles
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DOI：
10.3109/03009742.2011.605391
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发表时间：
2012-01-01
影响因子：
2.1
通讯作者：
Matsuyama, T.
中科院分区：
文献类型：
--
作者：
Tsuneyoshi, Y.;Tanaka, M.;Matsuyama, T.
目的：方法：采用流式细胞术检测骨关节炎（OA）滑膜组织中叶酸受体（FR）-β +巨噬细胞的表型分布及其M1/M2表达谱，并与类风湿关节炎（RA）滑膜组织及OA和RA滑膜组织中CD 163+巨噬细胞进行比较。通过免疫荧光显微镜检查FR-β +巨噬细胞在OA和RA滑膜组织中的分布。免疫组化双标法检测RA和OA滑膜组织中FR-β +巨噬细胞表达肿瘤坏死因子（TNF）-α、诱导型一氧化氮合酶（iNOS）、白细胞介素（IL）-10和转化生长因子（TGF）-β。与RA滑膜组织相比，OA中滑膜单核细胞（MNC）中CD 163-FR-β +细胞的比例增加。来自OA滑膜组织的FR-β（高）巨噬细胞代表了大多数叶酸结合细胞。结论：RA和OA患者滑膜组织中FR-β +和CD 163+巨噬细胞的分布和M1/M2表达谱不同。因此，这些发现强调了使用表面标志物FR-β和CD 163的M1/M2范例是对巨噬细胞亚群的过度简化。存在于OA滑膜巨噬细胞上的功能性FR-β为OA的诊断和治疗提供了潜在的工具。
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.