Myeloid Suppressor Cells Accumulate and Regulate Blood Pressure in Hypertension

Circ Res. 2015 Oct 23;117(10):858-69. doi: 10.1161/CIRCRESAHA.115.306539. Epub 2015 Aug 20.

Abstract

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 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.

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.

Keywords: T-lymphocytes; hypertension; inflammation; leukocytes; reactive oxygen species.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • NG-Nitroarginine Methyl Ester
  • Nephritis / immunology*
  • Nephritis / metabolism
  • Nephritis / physiopathology
  • Nephritis / prevention & control
  • Signal Transduction
  • Sodium, Dietary
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Time Factors

Substances

  • Antigens, Ly
  • CD11b Antigen
  • Inflammation Mediators
  • Ly6G antigen, mouse
  • Membrane Glycoproteins
  • Sodium, Dietary
  • Angiotensin II
  • Hydrogen Peroxide
  • Cybb protein, mouse
  • NADPH Oxidase 2
  • NADPH Oxidases
  • NG-Nitroarginine Methyl Ester