Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Arthritis Res Ther. 2012 Apr 11;14(2):R74. doi: 10.1186/ar3796.
Synovial tissue macrophages play a key role in chronic inflammatory arthritis, but the contribution of different macrophage subsets in this process remains largely unknown. The main in vitro polarized macrophage subsets are classically (M1) and alternatively (M2) activated macrophages, the latter comprising interleukin (IL)-4 and IL-10 polarized cells. Here, we aimed to evaluate the polarization status of synovial macrophages in spondyloarthritis (SpA) and rheumatoid arthritis (RA).
Expression of polarization markers on synovial macrophages, peripheral blood monocytes, and in vitro polarized monocyte-derived macrophages from SpA versus RA patients was assessed by immunohistochemistry and flow cytometry, respectively. The polarization status of the intimal lining layer and the synovial sublining macrophages was assessed by double immunofluorescence staining.
The expression of the IL-10 polarization marker cluster of differentiation 163 (CD163) was increased in SpA compared with RA intimal lining layer, but no differences were found in other M1 and M2 markers between the diseases. Furthermore, no significant phenotypic differences in monocytes and in vitro polarized monocyte-derived macrophages were seen between SpA, RA, and healthy controls, indicating that the differential CD163 expression does not reflect a preferential M2 polarization in SpA. More detailed analysis of intimal lining layer macrophages revealed a strong co-expression of the IL-10 polarization markers CD163 and cluster of differentiation 32 (CD32) but not any of the other markers in both SpA and RA. In contrast, synovial sublining macrophages had a more heterogeneous phenotype, with a majority of cells co-expressing M1 and M2 markers.
The intimal lining layer but not synovial sublining macrophages display an IL-10 polarized-like phenotype, with increased CD163 expression in SpA versus RA synovitis. These differences in the distribution of the polarized macrophage subset may contribute to the outcome of chronic synovitis.
滑膜组织中的巨噬细胞在慢性炎症性关节炎中起着关键作用，但在这个过程中不同巨噬细胞亚群的作用在很大程度上尚不清楚。主要的体外极化巨噬细胞亚群是经典（M1）和替代（M2）激活的巨噬细胞，后者包括白细胞介素（IL）-4 和 IL-10 极化细胞。在这里，我们旨在评估脊柱关节炎（SpA）和类风湿关节炎（RA）中滑膜巨噬细胞的极化状态。
通过免疫组织化学和流式细胞术分别评估 SpA 和 RA 患者滑膜巨噬细胞、外周血单核细胞和体外极化的单核细胞衍生巨噬细胞的极化标志物表达。通过双重免疫荧光染色评估内膜衬里层和滑膜下衬里层巨噬细胞的极化状态。
与 RA 相比，SpA 的内膜衬里层中白细胞介素 10 极化标志物 CD163 的表达增加，但两种疾病之间其他 M1 和 M2 标志物无差异。此外，SpA、RA 和健康对照组之间的单核细胞和体外极化的单核细胞衍生巨噬细胞之间没有明显的表型差异，表明差异 CD163 表达并不反映 SpA 中优先的 M2 极化。对内膜衬里层巨噬细胞的更详细分析显示，IL-10 极化标志物 CD163 和 CD32 在 SpA 和 RA 中强烈共表达，但其他标志物均不表达。相比之下，滑膜下衬里层巨噬细胞具有更异质的表型，大多数细胞共表达 M1 和 M2 标志物。
内膜衬里层而非滑膜下衬里层巨噬细胞显示出 IL-10 极化样表型，SpA 滑膜炎中 CD163 表达增加。这种极化巨噬细胞亚群分布的差异可能有助于慢性滑膜炎的结局。
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