AT₁ receptor-mediated angiotensin II activation and chemotaxis of T lymphocytes
2011
Silva-Filho, João Luiz | Souza, Mariana Conceição | Henriques, Maria das Graças | Morrot, Alexandre | Savino, W. (Wilson) | Nunes, Marise Pinheiro | Caruso-Neves, Celso | Pinheiro, Ana Acacia Sá
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 10⁻⁸M Ang II did not change any of the parameters evaluated. However, 10⁻⁶M 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, 10⁻⁶M captopril, an angiotensin-converting enzyme inhibitor had similar effects to Ang II, however its effects were reverted by exogenous Ang II (10⁻⁸M). None of these responses was modified by 10⁻⁷M 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.
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