Shah Kandarp H, Shi Peng, Giani Jorge F, Janjulia Tea, Bernstein Ellen A, Li You, Zhao Tuantuan, Harrison David G, Bernstein Kenneth E, Shen Xiao Z
From the Departments of Biomedical Sciences (K.H.S., J.F.G., T.J., E.A.B., T.Z., K.E.B., X.Z.S.), Pathology (K.E.B., X.Z.S.), and Neurology (P.S., Y.L.), Cedars-Sinai Medical Center, Los Angeles, CA; and Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (D.G.H).
Circ Res. 2015 Oct 23;117(10):858-69. doi: 10.1161/CIRCRESAHA.115.306539. Epub 2015 Aug 20.
Chronic inflammation is a major contributor to the progressive pathology of hypertension, and T-cell activation is required for the genesis of hypertension. However, the precise role of myeloid cells in this process is unclear.
To characterize and understand the role of peripheral myeloid cells in the development of hypertension.
We examined myeloid cells in the periphery of hypertensive mice and found that increased numbers of CD11b(+)Gr1(+) myeloid cells in blood and the spleen are a characteristic of 3 murine models of experimental hypertension (angiotensin II, L-NG-nitroarginine methyl ester, and high salt). These cells express surface markers and transcription factors associated with immaturity and immunosuppression. Also, they produce hydrogen peroxide to suppress T-cell activation. These are characteristics of myeloid-derived suppressor cells (MDSCs). Depletion of hypertensive MDSCs increased blood pressure and renal inflammation. In contrast, adoptive transfer of wild-type MDSCs to hypertensive mice reduced blood pressure, whereas the transfer of nicotinamide adenine dinucleotide phosphate oxidase 2-deficient MDSCs did not.
The accumulation of MDSCs is a characteristic of experimental models of hypertension. MDSCs limit inflammation and the increase of blood pressure through the production of hydrogen peroxide.
慢性炎症是高血压进行性病理变化的主要促成因素，高血压的发生需要T细胞激活。然而，髓样细胞在此过程中的具体作用尚不清楚。
表征并了解外周髓样细胞在高血压发展中的作用。
我们检查了高血压小鼠外周的髓样细胞，发现血液和脾脏中CD11b(+)Gr1(+)髓样细胞数量增加是3种实验性高血压小鼠模型（血管紧张素II、L-NG-硝基精氨酸甲酯和高盐）的一个特征。这些细胞表达与不成熟和免疫抑制相关的表面标志物和转录因子。此外，它们产生过氧化氢以抑制T细胞激活。这些是髓样来源的抑制细胞（MDSCs）的特征。清除高血压小鼠的MDSCs会升高血压并加剧肾脏炎症。相反，将野生型MDSCs过继转移到高血压小鼠中可降低血压，而转移烟酰胺腺嘌呤二核苷酸磷酸氧化酶2缺陷型MDSCs则没有这种效果。
MDSCs的积累是高血压实验模型的一个特征。MDSCs通过产生过氧化氢来限制炎症和血压升高。
