About this item:

504 Views | 0 Downloads

Author Notes:

Address for reprint requests and other correspondence: D. G Harrison, Cardiology Div., Emory Univ. School of Medicine, 1639 Pierce Dr., Atlanta, GA 30322 (e-mail: dharr02@emory.edu)

Subjects:

Research Funding:

This study was supported by National Institutes of Health (NIH) Grants HL-390006, AR-42527, AI-44142, EY-11916, AR-41974, NIH Program Project Grants HL-58000 and P01075209, and a Department of Veterans Affairs Merit Grant.

Keywords:

  • cytokines
  • TNF-α
  • electron spin resonance
  • adoptive transfer
  • NADPH oxidase
  • superoxide

Regulation of T-cell function by endogenously produced angiotensin II

Tools:

Journal Title:

AJP - Regulatory, Integrative and Comparative Physiology

Volume:

Volume 296, Number 2

Publisher:

, Pages R208-R216

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2009, American Physiological Society

Export to EndNote