title: AT1 receptor-mediated angiotensin II activation and chemotaxis of T lymphocytes.
abstract: Angiotensin II (Ang II), a central renin-angiotensin system (RAS) effector molecule, and its receptors, AT(1) and AT(2), 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 AT(1) 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 AT(2) 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 AT(1) receptor activation. Moreover, AT(1) receptor expression is 10-fold higher in activated T lymphocytes compared with naive cells, but AT(2) receptor expression did not change after T cell receptor triggering.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: João Luiz
authors.initials: JL
authors.lastname: Silva-Filho
authors.forename: Mariana Conceição
authors.initials: MC
authors.lastname: Souza
authors.forename: Maria das Graças
authors.initials: Md
authors.lastname: Henriques
authors.forename: Alexandre
authors.initials: A
authors.lastname: Morrot
authors.forename: Wilson
authors.initials: W
authors.lastname: Savino
authors.forename: Marise Pinheiro
authors.initials: MP
authors.lastname: Nunes
authors.forename: Celso
authors.initials: C
authors.lastname: Caruso-Neves
authors.forename: Ana Acacia Sá
authors.initials: AA
authors.lastname: Pinheiro
mesh_terms: D000804:Angiotensin II / Q000276:immunology* / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II