Age-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell development
Само за регистроване кориснике
2010
Аутори
Leposavić, GordanaPešić, Vesna
Stojić-Vukanić, Zorica
Radojević, Katarina
Arsenović-Ranin, Nevena
Kosec, Duško
Perišić, M.
Pilipović, Ivan
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Alpha(1)-adrenoceptors (alpha(1)-ARs) are involved in neuro-thymic and thymic intercellular communications, and consequently modulation of T-cell development. Ageing is associated with a number of changes in noradrenergic neuro-effector transmission, and possibly intercellular noradrenaline (NA)-mediated communication resulting in altered responses of target cells to NA. Thus, in old animals an altered NA modulation of thymopoiesis via alpha(1)-ARs may be expected. To test this hypothesis, in old and young adult Wistar rats we examined: 1) thymic NA levels, density of noradrenergic innervation and NA synthesizing cells, as well as alpha(1)-AR expression, and 2) then the effects of 14-day-long treatment with the alpha(1)-AR blocker, urapidil, on thymocyte development. Overall, the first part of study suggested augmented NA signalling to thymic cells via alpha(1)-ARs due to increased NA availability and alpha(1)-AR thymocyte surface density in old rats. The second part of study supported... this assumption. Namely, although in rats of both ages urapidil affected the same thymocyte developmental steps ultimately leading to changes in the relative number of the most mature single positive TCR alpha beta(high) thymocytes, its effects were generally more prominent in old animals. Following urapidil treatment, the percentages of CD4+CD8- cells, including those showing a regulatory CD4+CD25+RT6.1- phenotype, were increased, while CD4-CD8+ cells decreased. In old rats, an augmented thymic escape of immature CD4+CD8+ cells was also registered. In rats of both ages the thymic changes were accompanied by alterations in the proportions of major cell populations in the T-lymphocyte compartment of both peripheral blood and spleen, leading to an increase in the CD4+/CD8+ T-cell ratio. These alterations were also more pronounced in old rats. Moreover, in old rats following urapidil treatment the proportion of TCR alpha beta + cells in the periphery was slightly greater reflecting, most likely, partly enhanced thymic production of regulatory CD161 +TCR alpha beta + cells. Thus, the study indirectly suggests an age-associated increase in the basal alpha(1)-AR-mediated inhibitory influence of NA on thymopoiesis.
Кључне речи:
Ageing / Noradrenaline / alpha -adrenoceptors / Rat thymus / T-cell developmentИзвор:
Experimental Gerontology, 2010, 45, 12, 918-935Издавач:
- Pergamon-Elsevier Science Ltd, Oxford
Финансирање / пројекти:
DOI: 10.1016/j.exger.2010.08.011
ISSN: 0531-5565
PubMed: 20800673
WoS: 000285368200002
Scopus: 2-s2.0-78449280616
Институција/група
PharmacyTY - JOUR AU - Leposavić, Gordana AU - Pešić, Vesna AU - Stojić-Vukanić, Zorica AU - Radojević, Katarina AU - Arsenović-Ranin, Nevena AU - Kosec, Duško AU - Perišić, M. AU - Pilipović, Ivan PY - 2010 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1358 AB - Alpha(1)-adrenoceptors (alpha(1)-ARs) are involved in neuro-thymic and thymic intercellular communications, and consequently modulation of T-cell development. Ageing is associated with a number of changes in noradrenergic neuro-effector transmission, and possibly intercellular noradrenaline (NA)-mediated communication resulting in altered responses of target cells to NA. Thus, in old animals an altered NA modulation of thymopoiesis via alpha(1)-ARs may be expected. To test this hypothesis, in old and young adult Wistar rats we examined: 1) thymic NA levels, density of noradrenergic innervation and NA synthesizing cells, as well as alpha(1)-AR expression, and 2) then the effects of 14-day-long treatment with the alpha(1)-AR blocker, urapidil, on thymocyte development. Overall, the first part of study suggested augmented NA signalling to thymic cells via alpha(1)-ARs due to increased NA availability and alpha(1)-AR thymocyte surface density in old rats. The second part of study supported this assumption. Namely, although in rats of both ages urapidil affected the same thymocyte developmental steps ultimately leading to changes in the relative number of the most mature single positive TCR alpha beta(high) thymocytes, its effects were generally more prominent in old animals. Following urapidil treatment, the percentages of CD4+CD8- cells, including those showing a regulatory CD4+CD25+RT6.1- phenotype, were increased, while CD4-CD8+ cells decreased. In old rats, an augmented thymic escape of immature CD4+CD8+ cells was also registered. In rats of both ages the thymic changes were accompanied by alterations in the proportions of major cell populations in the T-lymphocyte compartment of both peripheral blood and spleen, leading to an increase in the CD4+/CD8+ T-cell ratio. These alterations were also more pronounced in old rats. Moreover, in old rats following urapidil treatment the proportion of TCR alpha beta + cells in the periphery was slightly greater reflecting, most likely, partly enhanced thymic production of regulatory CD161 +TCR alpha beta + cells. Thus, the study indirectly suggests an age-associated increase in the basal alpha(1)-AR-mediated inhibitory influence of NA on thymopoiesis. PB - Pergamon-Elsevier Science Ltd, Oxford T2 - Experimental Gerontology T1 - Age-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell development VL - 45 IS - 12 SP - 918 EP - 935 DO - 10.1016/j.exger.2010.08.011 ER -
@article{ author = "Leposavić, Gordana and Pešić, Vesna and Stojić-Vukanić, Zorica and Radojević, Katarina and Arsenović-Ranin, Nevena and Kosec, Duško and Perišić, M. and Pilipović, Ivan", year = "2010", abstract = "Alpha(1)-adrenoceptors (alpha(1)-ARs) are involved in neuro-thymic and thymic intercellular communications, and consequently modulation of T-cell development. Ageing is associated with a number of changes in noradrenergic neuro-effector transmission, and possibly intercellular noradrenaline (NA)-mediated communication resulting in altered responses of target cells to NA. Thus, in old animals an altered NA modulation of thymopoiesis via alpha(1)-ARs may be expected. To test this hypothesis, in old and young adult Wistar rats we examined: 1) thymic NA levels, density of noradrenergic innervation and NA synthesizing cells, as well as alpha(1)-AR expression, and 2) then the effects of 14-day-long treatment with the alpha(1)-AR blocker, urapidil, on thymocyte development. Overall, the first part of study suggested augmented NA signalling to thymic cells via alpha(1)-ARs due to increased NA availability and alpha(1)-AR thymocyte surface density in old rats. The second part of study supported this assumption. Namely, although in rats of both ages urapidil affected the same thymocyte developmental steps ultimately leading to changes in the relative number of the most mature single positive TCR alpha beta(high) thymocytes, its effects were generally more prominent in old animals. Following urapidil treatment, the percentages of CD4+CD8- cells, including those showing a regulatory CD4+CD25+RT6.1- phenotype, were increased, while CD4-CD8+ cells decreased. In old rats, an augmented thymic escape of immature CD4+CD8+ cells was also registered. In rats of both ages the thymic changes were accompanied by alterations in the proportions of major cell populations in the T-lymphocyte compartment of both peripheral blood and spleen, leading to an increase in the CD4+/CD8+ T-cell ratio. These alterations were also more pronounced in old rats. Moreover, in old rats following urapidil treatment the proportion of TCR alpha beta + cells in the periphery was slightly greater reflecting, most likely, partly enhanced thymic production of regulatory CD161 +TCR alpha beta + cells. Thus, the study indirectly suggests an age-associated increase in the basal alpha(1)-AR-mediated inhibitory influence of NA on thymopoiesis.", publisher = "Pergamon-Elsevier Science Ltd, Oxford", journal = "Experimental Gerontology", title = "Age-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell development", volume = "45", number = "12", pages = "918-935", doi = "10.1016/j.exger.2010.08.011" }
Leposavić, G., Pešić, V., Stojić-Vukanić, Z., Radojević, K., Arsenović-Ranin, N., Kosec, D., Perišić, M.,& Pilipović, I.. (2010). Age-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell development. in Experimental Gerontology Pergamon-Elsevier Science Ltd, Oxford., 45(12), 918-935. https://doi.org/10.1016/j.exger.2010.08.011
Leposavić G, Pešić V, Stojić-Vukanić Z, Radojević K, Arsenović-Ranin N, Kosec D, Perišić M, Pilipović I. Age-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell development. in Experimental Gerontology. 2010;45(12):918-935. doi:10.1016/j.exger.2010.08.011 .
Leposavić, Gordana, Pešić, Vesna, Stojić-Vukanić, Zorica, Radojević, Katarina, Arsenović-Ranin, Nevena, Kosec, Duško, Perišić, M., Pilipović, Ivan, "Age-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell development" in Experimental Gerontology, 45, no. 12 (2010):918-935, https://doi.org/10.1016/j.exger.2010.08.011 . .