Myeloid Suppressor Cells Accumulate and Regulate Blood Pressure in Hypertension

• Published in: Circulation research Vol. 117; no. 10; pp. 858 - 869
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 23.10.2015
• Subjects: Adoptive Transfer; Angiotensin II; Animals; Antigens, Ly - metabolism; Blood Pressure; CD11b Antigen - metabolism; Cells, Cultured; Disease Models, Animal; Hydrogen Peroxide - metabolism; Hypertension - immunology; Hypertension - metabolism; Hypertension - physiopathology; Hypertension - prevention & control; Immune Tolerance; Inflammation Mediators - metabolism; Lymphocyte Activation; Male; Membrane Glycoproteins - deficiency; Membrane Glycoproteins - genetics; Mice, Inbred C57BL; Mice, Knockout; Myeloid Cells - immunology; Myeloid Cells - metabolism; Myeloid Cells - transplantation; NADPH Oxidase 2; NADPH Oxidases - deficiency; NADPH Oxidases - genetics; Nephritis - immunology; Nephritis - metabolism; Nephritis - physiopathology; Nephritis - prevention & control; NG-Nitroarginine Methyl Ester; Signal Transduction; Sodium, Dietary; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Time Factors; leukocytes; T-lymphocytes; inflammation; hypertension; reactive oxygen species
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/CIRCRESAHA.115.306539

RATIONALE: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. OBJECTIVE:To characterize and understand the role of peripheral myeloid cells in the development of hypertension. METHODS AND RESULTS:We examined myeloid cells in the periphery of hypertensive mice and found that increased numbers of CD11bGr1 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. CONCLUSION: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.