title: Myeloid Suppressor Cells Accumulate and Regulate Blood Pressure in Hypertension.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: 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).
authors: Kandarp H
authors: KH
authors: Shah
authors: 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).
authors: Peng
authors: P
authors: Shi
authors: 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).
authors: Jorge F
authors: JF
authors: Giani
authors: 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).
authors: Tea
authors: T
authors: Janjulia
authors: 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).
authors: Ellen A
authors: EA
authors: Bernstein
authors: 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).
authors: You
authors: Y
authors: Li
authors: 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).
authors: Tuantuan
authors: T
authors: Zhao
authors: 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).
authors: David G
authors: DG
authors: Harrison
authors: 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).
authors: Kenneth E
authors: KE
authors: Bernstein
authors: 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). xiao.shen@cshs.org.
authors: Xiao Z
authors: XZ
authors: Shen
mesh_terms: D019264:Adoptive Transfer; D000804:Angiotensin II; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001794:Blood Pressure; D039481:CD11b Antigen / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006861:Hydrogen Peroxide / Q000378:metabolism; D006973:Hypertension / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D007108:Immune Tolerance; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics; D019331:NG-Nitroarginine Methyl Ester; D009393:Nephritis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D015398:Signal Transduction; D012982:Sodium, Dietary; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D000950:Antigens, Ly; D039481:CD11b Antigen; D018836:Inflammation Mediators; C480309:Ly6G antigen, mouse; D008562:Membrane Glycoproteins; D012982:Sodium, Dietary; D000804:Angiotensin II; D006861:Hydrogen Peroxide; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D019331:NG-Nitroarginine Methyl Ester
keywords: T-lymphocytes; hypertension; inflammation; leukocytes; reactive oxygen species