AT1 receptor-mediated angiotensin II activation and chemotaxis of T lymphocytes

Silva-Filho, J. L. , Souza, M. C., Henriques, M. d. G., Morrot, A., Savino, W., Nunes, M. P., Caruso-Neves, C. and Pinheiro, A. A. S. (2011) AT1 receptor-mediated angiotensin II activation and chemotaxis of T lymphocytes. Molecular Immunology, 48(15-16), pp. 1835-1843. (doi: 10.1016/j.molimm.2011.05.008) (PMID:21641648)

Abstract

Angiotensin II (Ang II), a central renin–angiotensin system (RAS) effector molecule, and its receptors, AT1 and AT2, have been shown to be involved in the inflammatory aspects of different diseases, however the cellular mechanisms underlying the regulation of immunity are not fully understood. In this work, using spleen-derived CD4+ and CD8+ T lymphocytes activated in vitro, we tested the influence of Ang II on different aspects of the T cell function, such as activation and adhesion/transmigration through endothelial basal membrane proteins. The addition of 10−8 M Ang II did not change any of the parameters evaluated. However, 10−6 M losartan, an AT1 receptor antagonist: (i) reduced the percentage of CD25+ and CD69+ cells of both subsets; (ii) inhibited adhesion of these cells to fibronectin or laminin by 53% or 76%, respectively and (iii) significantly reduced transmigration through fibronectin or laminin by 57% or 43%, respectively. In addition, 10−6 M captopril, an angiotensin-converting enzyme inhibitor had similar effects to Ang II, however its effects were reverted by exogenous Ang II (10−8 M). None of these responses was modified by 10−7 M PD123319, an AT2 antagonist. These data reinforce the notion of endogenous production of Ang II by T cells, which is important for T cell activation, and adhesion/transmigration induced on interaction with basal membrane proteins, possibly involving AT1 receptor activation. Moreover, AT1 receptor expression is 10-fold higher in activated T lymphocytes compared with naive cells, but AT2 receptor expression did not change after T cell receptor triggering.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Da Silva Filho, Dr Joao
• Authors: Silva-Filho, J. L., Souza, M. C., Henriques, M. d. G., Morrot, A., Savino, W., Nunes, M. P., Caruso-Neves, C., and Pinheiro, A. A. S.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Molecular Immunology
• Publisher: Elsevier
• ISSN: 0161-5890
• ISSN (Online): 1872-9142
• Published Online: 08 June 2011