Regulation of T-cell function by endogenously produced angiotensin II

Hoch, N. E., Guzik, T. J., Chen, W., Deans, T., Maalouf, S. A., Gratze, P., Weyand, C. and Harrison, D. G. (2009) Regulation of T-cell function by endogenously produced angiotensin II. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 296(2), R208-R216. (doi: 10.1152/ajpregu.90521.2008) (PMID:19073907) (PMCID:PMC2643984)

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Abstract

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-α. Inhibition of T-cell ACE reduced TNF-α 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-α production. We found that superoxide was a critical mediator of T-cell TNF-α 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-α production. These findings contribute to our understanding of how ANG II and T cells enhance inflammation in cardiovascular disease.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Guzik, Professor Tomasz
Authors: Hoch, N. E., Guzik, T. J., Chen, W., Deans, T., Maalouf, S. A., Gratze, P., Weyand, C., and Harrison, D. G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:American Journal of Physiology: Regulatory, Integrative and Comparative Physiology
Publisher:American Physiological Society
ISSN:0363-6119
ISSN (Online):1522-1490
Published Online:10 December 2008

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