M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis.
M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis.
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DOI：
10.3389/fimmu.2017.01958
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发表时间：
2017
影响因子：
7.3
通讯作者：
Kawakami A
中科院分区：
文献类型：
--
作者：
Fukui S;Iwamoto N;Takatani A;Igawa T;Shimizu T;Umeda M;Nishino A;Horai Y;Hirai Y;Koga T;Kawashiri SY;Tamai M;Ichinose K;Nakamura H;Origuchi T;Masuyama R;Kosai K;Yanagihara K;Kawakami A
我们研究了类风湿性关节炎 (RA) 患者 M1 单核细胞、M2 单核细胞、破骨细胞 (OC) 分化能力和临床特征之间的关系。从 RA 患者和健康供体中分离外周血单核细胞 (PBMC)，然后通过荧光激活细胞分选研究 M1 单核细胞或 M2 单核细胞的数量。我们还从 RA 患者和健康供体的 PBMC 中获取并培养 CD14 阳性细胞，以研究 OC 的体外分化。包括 40 名 RA 患者和 20 名健康捐献者。 22 名患者 (55%) 抗瓜氨酸蛋白抗体 (ACPA) 呈阳性。 M1/M2 比率中位数为 0.59（0.31-1.11，四分位距）。 RA患者和健康捐献者之间没有显着差异。 RA患者的M1/M2比值与体外分化的OC数呈正相关（ρ = 0.81，p < 0.001）。与 ACPA 阴性患者相比，ACPA 阳性患者的体内 M1/M2 比值显着更高（p = 0.028），体外 OC 数量显着更高（p = 0.005）。多变量回归分析显示，M1/M2 比值是体外破骨细胞生成的唯一显着贡献因素。 M1/M2比值>1（M1单核细胞相对较多）的RA患者比M1/M2比值≤1的RA患者具有更高的C反应蛋白和红细胞沉降率。在体外，M1 型单核细胞在脂多糖刺激下产生的白细胞介素 6 浓度高于 M2 单核细胞。 M1/M2 单核细胞失衡对 RA 患者的破骨细胞生成有重要影响。我们的研究结果以新的视角将 M1 和 M2 单核细胞亚群作为 RA 治疗的新靶点，以防止破骨细胞骨质破坏的进展。
We investigated the relationships among M1 monocytes, M2 monocytes, osteoclast (OC) differentiation ability, and clinical characteristics in patients with rheumatoid arthritis (RA). Peripheral blood mononuclear cells (PBMCs) were isolated from RA patients and healthy donors, and we then investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated cell sorting. We also obtained and cultured CD14-positive cells from PBMCs from RA patients and healthy donors to investigate OC differentiation in vitro. Forty RA patients and 20 healthy donors were included. Twenty-two patients (55%) were anticitrullinated protein antibody (ACPA) positive. The median M1/M2 ratio was 0.59 (0.31–1.11, interquartile range). There were no significant differences between the RA patients and healthy donors. There was a positive correlation between the M1/M2 ratio and the differentiated OC number in vitro in RA patients (ρ = 0.81, p < 0.001). The ACPA-positive patients had significantly higher M1/M2 ratios in vivo (p = 0.028) and significantly greater numbers of OCs in vitro (p = 0.005) than the ACPA-negative patients. Multivariable regression analysis revealed that the M1/M2 ratio was the sole significant contribution factor to in vitro osteoclastogenesis. RA patients with M1/M2 ratios >1 (having relatively more M1 monocytes) had higher C-reactive protein and erythrocyte sedimentation rates than RA patients with M1/M2 ratios ≤1. M1-dominant monocytes in vitro produced higher concentrations of interleukin-6 upon stimulation with lipopolysaccharide than M2 monocytes. M1/M2 monocytes imbalance strongly contributes to osteoclastogenesis of RA patients. Our findings cast M1 and M2 monocyte subsets in a new light as a new target of treatments for RA to prevent progression of osteoclastic bone destruction.
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DOI：
10.4049/jimmunol.0900473
发表时间：
2009-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Shaykhiev R;Krause A;Salit J;Strulovici-Barel Y;Harvey BG;O'Connor TP;Crystal RG
通讯作者：
Crystal RG
影响因子：
27.4
作者：
Clavel, Cyril;Ceccato, Laurie;Sebbag, Mireille
通讯作者：
Sebbag, Mireille
影响因子：
56.9
作者：
ROTHSCHILD, BM;TURNER, KR;DELUCA, MA
通讯作者：
DELUCA, MA
影响因子：
3.6
作者：
Medeiros, Leonardo T. L.;Peracoli, Jose C.;Peracoli, Maria T. S.
通讯作者：
Peracoli, Maria T. S.
影响因子：
3.1
作者：
Martinez, Fernando Oneissi;Sica, Antonio;Locati, Massimo
通讯作者：
Locati, Massimo