Regulation of T-cell function by endogenously produced angiotensin II.

Hoch NE, Guzik TJ, Chen W, Deans T, Maalouf SA, Gratze P, Weyand C, Harrison DG
Am J Physiol Regul Integr Comp Physiol. 2009 296 (2): R208-16

PMID: 19073907 · PMCID: PMC2643984 · DOI:10.1152/ajpregu.90521.2008

The adaptive immune response and, in particular, T cells have been shown to be important in the genesis of hypertension. In the present study, we sought to determine how the interplay between ANG II, NADPH oxidase, and reactive oxygen species modulates T cell activation and ultimately causes hypertension. We determined that T cells express angiotensinogen, the angiotensin I-converting enzyme, and renin and produce physiological levels of ANG II. AT1 receptors were primarily expressed intracellularly, and endogenously produced ANG II increased T-cell activation, expression of tissue homing markers, and production of the cytokine TNF-alpha. Inhibition of T-cell ACE reduced TNF-alpha production, indicating endogenously produced ANG II has a regulatory role in this process. Studies with specific antagonists and T cells from AT1R and AT2R-deficient mice indicated that both receptor subtypes contribute to TNF-alpha production. We found that superoxide was a critical mediator of T-cell TNF-alpha production, as this was significantly inhibited by polyethylene glycol (PEG)-SOD, but not PEG-catalase. Thus, T cells contain an endogenous renin-angiotensin system that modulates T-cell function, NADPH oxidase activity, and production of superoxide that, in turn, modulates TNF-alpha production. These findings contribute to our understanding of how ANG II and T cells enhance inflammation in cardiovascular disease.

MeSH Terms (31)

Adoptive Transfer Angiotensin II Angiotensin II Type 1 Receptor Blockers Angiotensin II Type 2 Receptor Blockers Angiotensinogen Animals Autocrine Communication Blood Pressure Catalase Cells, Cultured Homeodomain Proteins Imidazoles Infusion Pumps, Implantable Losartan Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Knockout NADPH Oxidases Peptidyl-Dipeptidase A Polyethylene Glycols Pyridines Receptor, Angiotensin, Type 1 Receptor, Angiotensin, Type 2 Renin Renin-Angiotensin System Superoxide Dismutase Superoxides T-Lymphocytes Time Factors Tumor Necrosis Factor-alpha

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