Characterization of thymocyte phenotypic alterations induced by long-lasting [beta]-adrenoceptor blockade in vivo and its effects on thymocyte proliferation and apoptosis

• Published in: Molecular and cellular biochemistry 2006-04, Vol.285 (1-2), p.87
• Main Authors: Leposavic, G, Arsenovic-ranin, N, Radojevic, K, Kosec, D, Pesic, V, Vidic-dankovic, B, Plecas-solarovic, B, Pilipovic, I
• Format: Article
• Language: English
• Subjects: Apoptosis; Immune response; Rodents
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-005-9059-5

Adult male Wistar rats were subjected to propranolol (P, 0.40 mg/100 g/day) or saline (S) administration (controls) over 14 days. The expression of major differentiation molecules on thymocytes and Thy-1 (CD90) molecules, which are shown to adjust thymocyte sensitivity to TCRαβ signaling, was studied. In addition, the sensitivity of thymocytes to induction of apoptosis and concanavalin A (Con A) signaling was estimated. The thymocytes from P-treated (PT) rats exhibited an increased sensitivity to induction of apoptosis, as well as to Con A stimulation. Furthermore, P treatment produced changes in the distribution of thymocyte subsets suggesting that more cells passed positive selection and further differentiated into mature CD4+ or CD8+ single positive (SP) TCRαβ^sup high^ cells. These changes may, at least partly, be related to the markedly increased density of Thy-1 surface expression on TCRαβ^sup low^ thymocytes from these rats. The increased frequency of cells expressing the CD4+25+ phenotype, which has been shown to be characteristic for regulatory cells in the thymus, may also indicate alterations in thymocyte selection following P treatment. Inasmuch as positive and negative selections play an important role in continuously reshaping the T-cell repertoire and maintaining tolerance, the hereby presented study suggests that pharmacological manipulations with β-AR signaling, or chemically evoked alterations in catecholamine release, may interfere with the regulation of thymocyte selection, and consequently with the immune response. (Mol Cell Biochem xxx: 1-13, 2005)[PUBLICATION ABSTRACT]