TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Rauski, Aleksandra
AU  - Kosec, Duško
AU  - Radojević, Katarina
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1197
AB  - A number of different experimental approaches have been used to elucidate the impact: of basal levels of adrenal gland-derived glucocorticoids (GCs) on T cell development, and thereby T cell-mediated immune responses. However, the relevance of the adrenal GCs to T cell development is still far from clear. This study was undertaken to explore the relevance of basal levels of GCs to T cell differentiation/maturation. Eight days post-adrenalectomy in adult male rats the thymocyte yield, apoptotic and proliferative rate and the relationship amongst major thymocyte subsets, as defined by TCR alpha beta/CD4/CD8 expression, were examined using flow cytometry. Adrenal GC deprivation decreased thymocyte apoptosis and altered the kinetics of T cell differentiation/maturation. In the adrenalectomized rats there was increased thymic hypercellularity and an over-representation of the CD4+CD8+ double positive (DP) TCR alpha beta(low) cells entering selection, as well as increased numbers of their DP TCR alpha beta(-) immediate precursors. These changes were accompanied with under-representation of the postselected DP TCR alpha beta(high) and the most mature CD4-CD8+ and, particularly, CD4+CD8-single positive (SP) TCR alpha beta(high) cells. This data suggests that withdrawal of adrenal GCs produces alterations in the thymocyte selection processes, possibly affecting the diversity of functional T cell repertoire and generation of potentially self-reactive cells as indicated by the reduced proportion and number of CD4-CD8- double negative TCR alpha beta(high) cells. In addition, it indicates that GCs influence the post-selection maturation of thymocytes and plays a regulatory role in controlling the ratio of mature CD4+CD8-/CD4-CD8+ SP TCR alpha beta(high) cells. Exp Biol Med 234:1067-1074, 2009
PB  - Royal Soc Medicine Press Ltd, London
T2  - Experimental Biology and Medicine
T1  - Dysregulation of T-Cell Development in Adrenal Glucocorticoid-Deprived Rats
VL  - 234
IS  - 9
SP  - 1067
EP  - 1074
DO  - 10.3181/0902-RM-63
ER  - 

@article{
author = "Stojić-Vukanić, Zorica and Rauski, Aleksandra and Kosec, Duško and Radojević, Katarina and Pilipović, Ivan and Leposavić, Gordana",
year = "2009",
abstract = "A number of different experimental approaches have been used to elucidate the impact: of basal levels of adrenal gland-derived glucocorticoids (GCs) on T cell development, and thereby T cell-mediated immune responses. However, the relevance of the adrenal GCs to T cell development is still far from clear. This study was undertaken to explore the relevance of basal levels of GCs to T cell differentiation/maturation. Eight days post-adrenalectomy in adult male rats the thymocyte yield, apoptotic and proliferative rate and the relationship amongst major thymocyte subsets, as defined by TCR alpha beta/CD4/CD8 expression, were examined using flow cytometry. Adrenal GC deprivation decreased thymocyte apoptosis and altered the kinetics of T cell differentiation/maturation. In the adrenalectomized rats there was increased thymic hypercellularity and an over-representation of the CD4+CD8+ double positive (DP) TCR alpha beta(low) cells entering selection, as well as increased numbers of their DP TCR alpha beta(-) immediate precursors. These changes were accompanied with under-representation of the postselected DP TCR alpha beta(high) and the most mature CD4-CD8+ and, particularly, CD4+CD8-single positive (SP) TCR alpha beta(high) cells. This data suggests that withdrawal of adrenal GCs produces alterations in the thymocyte selection processes, possibly affecting the diversity of functional T cell repertoire and generation of potentially self-reactive cells as indicated by the reduced proportion and number of CD4-CD8- double negative TCR alpha beta(high) cells. In addition, it indicates that GCs influence the post-selection maturation of thymocytes and plays a regulatory role in controlling the ratio of mature CD4+CD8-/CD4-CD8+ SP TCR alpha beta(high) cells. Exp Biol Med 234:1067-1074, 2009",
publisher = "Royal Soc Medicine Press Ltd, London",
journal = "Experimental Biology and Medicine",
title = "Dysregulation of T-Cell Development in Adrenal Glucocorticoid-Deprived Rats",
volume = "234",
number = "9",
pages = "1067-1074",
doi = "10.3181/0902-RM-63"
}

Stojić-Vukanić, Z., Rauski, A., Kosec, D., Radojević, K., Pilipović, I.,& Leposavić, G.. (2009). Dysregulation of T-Cell Development in Adrenal Glucocorticoid-Deprived Rats. in Experimental Biology and Medicine
Royal Soc Medicine Press Ltd, London., 234(9), 1067-1074.
https://doi.org/10.3181/0902-RM-63

Stojić-Vukanić Z, Rauski A, Kosec D, Radojević K, Pilipović I, Leposavić G. Dysregulation of T-Cell Development in Adrenal Glucocorticoid-Deprived Rats. in Experimental Biology and Medicine. 2009;234(9):1067-1074.
doi:10.3181/0902-RM-63 .

Stojić-Vukanić, Zorica, Rauski, Aleksandra, Kosec, Duško, Radojević, Katarina, Pilipović, Ivan, Leposavić, Gordana, "Dysregulation of T-Cell Development in Adrenal Glucocorticoid-Deprived Rats" in Experimental Biology and Medicine, 234, no. 9 (2009):1067-1074,
https://doi.org/10.3181/0902-RM-63 . .

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Rauski, Aleksandra
AU  - Radojević, Katarina
AU  - Kosec, Duško
AU  - Stanojević, S.
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2007
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/893
AB  - As glucocorticoids influence both catecholamine synthesis and adrenoceptor expression by immune cells, the current study was undertaken to distinguish their direct effects on the development of experimental allergic encephalomyelitis from those induced by alteration of catecholamine signaling. We examined the influence of 16-day-long beta-adrenoceptor blockade with propranolol (0.40 mg/100 g body weight/day, s.c.) beginning 3 days before immunization on the development of experimental allergic encephalomyelitis in adrenalectomized (7 days before immunization) and in non-operated male Dark Agouti rats. Adrenalectomy aggravated the clinical course of experimental allergic encephalomyelitis. In contrast, propranolol attenuated both the clinical signs of the disease and decreased the number of lesions in the spinal cord. Furthermore, propranolol prevented adrenalectomy-induced aggravation of the disease course without affecting mortality. We also found that the percentage of CD4(+)CD25(+) T lymphocytes (recently activated or regulatory cells) was increased in peripheral blood of experimental allergic encephalomyelitis rats over that in the corresponding non-immunized and bovine serum albumin immunized rats. However, the percentage of these cells was reduced in adrenalectomized and/or propranolol-treated experimental allergic encephalomyelitis rats compared to control experimental allergic encephalomyelitis rats. Our findings, coupled with the clinical course of the disease and the underlying pathomorphological changes, clearly suggest that differential mechanisms were responsible for the changes in the percentage of CD4(+)CD25(+) T lymphocytes in propranolol-treated adrenalectomized rats and only propranolol-treated rats with experimental allergic encephalomyelitis. Our results, when viewed globally, indicate that: i) beta-adrenoceptor-dependent mechanisms are involved in the immunopathogenesis of experimental allergic encephalomyelitis, ii) experimental allergic encephalomyelitis has a more severe course in adrenalectomized rats and iii) beta-adrenoceptor-mediated mechanisms operate in adrenalectomy-induced aggravation of the disease.
PB  - Elsevier Science BV, Amsterdam
T2  - European Journal of Pharmacology
T1  - beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats
VL  - 577
IS  - 1-3
SP  - 170
EP  - 182
DO  - 10.1016/j.ejphar.2007.08.021
ER  - 

@article{
author = "Dimitrijević, Mirjana and Rauski, Aleksandra and Radojević, Katarina and Kosec, Duško and Stanojević, S. and Pilipović, Ivan and Leposavić, Gordana",
year = "2007",
abstract = "As glucocorticoids influence both catecholamine synthesis and adrenoceptor expression by immune cells, the current study was undertaken to distinguish their direct effects on the development of experimental allergic encephalomyelitis from those induced by alteration of catecholamine signaling. We examined the influence of 16-day-long beta-adrenoceptor blockade with propranolol (0.40 mg/100 g body weight/day, s.c.) beginning 3 days before immunization on the development of experimental allergic encephalomyelitis in adrenalectomized (7 days before immunization) and in non-operated male Dark Agouti rats. Adrenalectomy aggravated the clinical course of experimental allergic encephalomyelitis. In contrast, propranolol attenuated both the clinical signs of the disease and decreased the number of lesions in the spinal cord. Furthermore, propranolol prevented adrenalectomy-induced aggravation of the disease course without affecting mortality. We also found that the percentage of CD4(+)CD25(+) T lymphocytes (recently activated or regulatory cells) was increased in peripheral blood of experimental allergic encephalomyelitis rats over that in the corresponding non-immunized and bovine serum albumin immunized rats. However, the percentage of these cells was reduced in adrenalectomized and/or propranolol-treated experimental allergic encephalomyelitis rats compared to control experimental allergic encephalomyelitis rats. Our findings, coupled with the clinical course of the disease and the underlying pathomorphological changes, clearly suggest that differential mechanisms were responsible for the changes in the percentage of CD4(+)CD25(+) T lymphocytes in propranolol-treated adrenalectomized rats and only propranolol-treated rats with experimental allergic encephalomyelitis. Our results, when viewed globally, indicate that: i) beta-adrenoceptor-dependent mechanisms are involved in the immunopathogenesis of experimental allergic encephalomyelitis, ii) experimental allergic encephalomyelitis has a more severe course in adrenalectomized rats and iii) beta-adrenoceptor-mediated mechanisms operate in adrenalectomy-induced aggravation of the disease.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "European Journal of Pharmacology",
title = "beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats",
volume = "577",
number = "1-3",
pages = "170-182",
doi = "10.1016/j.ejphar.2007.08.021"
}

Dimitrijević, M., Rauski, A., Radojević, K., Kosec, D., Stanojević, S., Pilipović, I.,& Leposavić, G.. (2007). beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats. in European Journal of Pharmacology
Elsevier Science BV, Amsterdam., 577(1-3), 170-182.
https://doi.org/10.1016/j.ejphar.2007.08.021

Dimitrijević M, Rauski A, Radojević K, Kosec D, Stanojević S, Pilipović I, Leposavić G. beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats. in European Journal of Pharmacology. 2007;577(1-3):170-182.
doi:10.1016/j.ejphar.2007.08.021 .

Dimitrijević, Mirjana, Rauski, Aleksandra, Radojević, Katarina, Kosec, Duško, Stanojević, S., Pilipović, Ivan, Leposavić, Gordana, "beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats" in European Journal of Pharmacology, 577, no. 1-3 (2007):170-182,
https://doi.org/10.1016/j.ejphar.2007.08.021 . .

TY  - CONF
AU  - Rauski, Aleksandra
AU  - Kosec, Duško
AU  - Leposavić, Gordana
PY  - 2004
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/521
PB  - Elsevier Science BV, Amsterdam
C3  - Journal of Neuroimmunology
T1  - Catecholamines influence development of EAE
VL  - 154
IS  - 1-2
SP  - 86
EP  - 86
UR  - https://hdl.handle.net/21.15107/rcub_farfar_521
ER  - 

@conference{
author = "Rauski, Aleksandra and Kosec, Duško and Leposavić, Gordana",
year = "2004",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Neuroimmunology",
title = "Catecholamines influence development of EAE",
volume = "154",
number = "1-2",
pages = "86-86",
url = "https://hdl.handle.net/21.15107/rcub_farfar_521"
}

Rauski, A., Kosec, D.,& Leposavić, G.. (2004). Catecholamines influence development of EAE. in Journal of Neuroimmunology
Elsevier Science BV, Amsterdam., 154(1-2), 86-86.
https://hdl.handle.net/21.15107/rcub_farfar_521

Rauski A, Kosec D, Leposavić G. Catecholamines influence development of EAE. in Journal of Neuroimmunology. 2004;154(1-2):86-86.
https://hdl.handle.net/21.15107/rcub_farfar_521 .

Rauski, Aleksandra, Kosec, Duško, Leposavić, Gordana, "Catecholamines influence development of EAE" in Journal of Neuroimmunology, 154, no. 1-2 (2004):86-86,
https://hdl.handle.net/21.15107/rcub_farfar_521 .

TY  - JOUR
AU  - Rauski, Aleksandra
AU  - Kosec, Duško
AU  - Vidić-Danković, Biljana
AU  - Plećaš-Solarović, Bosiljka
AU  - Leposavić, Gordana
PY  - 2003
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/466
AB  - The study revealed that β-adrenoceptor blockade with propranolol (0. 40 mg/l00 g/day, s.c.) in adult male DA rats: (i) increased the thymocyte proliferation and apoptosis, (ii) caused disturbances in kinetics of T cell differentiation leading to distinguishable changes in relative proportion of thymocytes at distinct maturational steps and to an expansion of the most mature single positive (CD4+, CD8+) thymocyte pool, (iii) affected the relative proportion of neither CD4+ nor CD8+ peripheral blood lymphocytes (PBL), and (iv) augmented the relative number of CD8+CD25+ cells. Thus, the results suggest the role of β-adrenoceptors) in fine-tuning of T cell maturation, and, possibly, distribution and activation of distinct PBL subsets.
PB  - Taylor and Francis Ltd.
T2  - International Journal of Neuroscience
T1  - Effects of beta-adrenoceptor blockade on the phenotypic characteristics of thymocytes and peripheral blood lymphocytes
VL  - 113
IS  - 12
SP  - 1653
EP  - 1673
DO  - 10.1080/00207450390245216
ER  - 

@article{
author = "Rauski, Aleksandra and Kosec, Duško and Vidić-Danković, Biljana and Plećaš-Solarović, Bosiljka and Leposavić, Gordana",
year = "2003",
abstract = "The study revealed that β-adrenoceptor blockade with propranolol (0. 40 mg/l00 g/day, s.c.) in adult male DA rats: (i) increased the thymocyte proliferation and apoptosis, (ii) caused disturbances in kinetics of T cell differentiation leading to distinguishable changes in relative proportion of thymocytes at distinct maturational steps and to an expansion of the most mature single positive (CD4+, CD8+) thymocyte pool, (iii) affected the relative proportion of neither CD4+ nor CD8+ peripheral blood lymphocytes (PBL), and (iv) augmented the relative number of CD8+CD25+ cells. Thus, the results suggest the role of β-adrenoceptors) in fine-tuning of T cell maturation, and, possibly, distribution and activation of distinct PBL subsets.",
publisher = "Taylor and Francis Ltd.",
journal = "International Journal of Neuroscience",
title = "Effects of beta-adrenoceptor blockade on the phenotypic characteristics of thymocytes and peripheral blood lymphocytes",
volume = "113",
number = "12",
pages = "1653-1673",
doi = "10.1080/00207450390245216"
}

Rauski, A., Kosec, D., Vidić-Danković, B., Plećaš-Solarović, B.,& Leposavić, G.. (2003). Effects of beta-adrenoceptor blockade on the phenotypic characteristics of thymocytes and peripheral blood lymphocytes. in International Journal of Neuroscience
Taylor and Francis Ltd.., 113(12), 1653-1673.
https://doi.org/10.1080/00207450390245216

Rauski A, Kosec D, Vidić-Danković B, Plećaš-Solarović B, Leposavić G. Effects of beta-adrenoceptor blockade on the phenotypic characteristics of thymocytes and peripheral blood lymphocytes. in International Journal of Neuroscience. 2003;113(12):1653-1673.
doi:10.1080/00207450390245216 .

Rauski, Aleksandra, Kosec, Duško, Vidić-Danković, Biljana, Plećaš-Solarović, Bosiljka, Leposavić, Gordana, "Effects of beta-adrenoceptor blockade on the phenotypic characteristics of thymocytes and peripheral blood lymphocytes" in International Journal of Neuroscience, 113, no. 12 (2003):1653-1673,
https://doi.org/10.1080/00207450390245216 . .

TY  - JOUR
AU  - Rauski, Aleksandra
AU  - Kosec, Duško
AU  - Vidić-Danković, Biljana
AU  - Radojević, Katarina
AU  - Plećaš-Solarović, Bosiljka
AU  - Leposavić, Gordana
PY  - 2003
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/425
AB  - The present study was undertaken in order to further clarify putative role of the adrenergic innervation in the regulation of the intrathymic T-cell maturation. For this purpose adult male DA rats were subjected to either 4-day- or 16-day-long propranolol treatment (0.40 mg propranolol/100 g/day, s.c.) and the expression of CD4/8/TCRalphabeta on thymocytes, as well as thymocyte proliferative and apoptotic index, was assessed in these animals by flow cytometric analysis. Propranolol treatment, in spite of duration, increased both the thymocyte proliferative and apoptotic index (vs. respective vehicle-treated controls). In 4-day-treated animals the thymus cellularity and thymus weight remained unaltered, while in 16-day-treated rats the values of both of these parameters were reduced (since increase in the thymocyte apoptotic index overcame that in the proliferative index). The treatments of both durations affected the thymocyte phenotypic profile in a similar pattern, but the changes were more pronounced in rats exposed to the treatment of longer duration. The relative proportion of the least mature CD4-8- double negative (DN) TCRalphabeta(-) cells was increased, those of thymocytes at distinct differentiational stages on the transitional route to the CD4+8+ double positive (DP) TCRalphabeta(low) stage decreased (all subsets of TCRalphabeta(-) in both groups of rats, and those. with low expression of TCRalphabeta in rats subjected to 16-day-long treatment) or unaltered (all subsets of TCRalphabeta(low) cells in 4-day-treated rats). Furthermore, the percentage of CD4+8+ DP TCRalphabeta(low) cells was significantly elevated, as well as those of the most mature CD4+8-TCRalphabeta(high) and CD4-8+TCRalphabeta(high) cells (the increase in the percentage of former was much more conspicuous than that of the latter), while the relative proportion of their direct detectable precursors (CD4+8+ DP TCRalphabeta(high)) Was reduced. Thus, the present study: i) further supports notion of pharmacological manipulation of adrenergic action as an efficient means in modulation of the T-cell development, and hence T-cell-dependent immune response, and ii) provides more specific insight into T-cell maturation sequence point/s particularly sensitive to beta-adrenoceptor ligand action.
PB  - Informa Healthcare, London
T2  - Immunopharmacology and Immunotoxicology
T1  - Thymopoiesis following chronic blockade of beta-adrenoceptors
VL  - 25
IS  - 4
SP  - 513
EP  - 528
DO  - 10.1081/IPH-120026437
ER  - 

@article{
author = "Rauski, Aleksandra and Kosec, Duško and Vidić-Danković, Biljana and Radojević, Katarina and Plećaš-Solarović, Bosiljka and Leposavić, Gordana",
year = "2003",
abstract = "The present study was undertaken in order to further clarify putative role of the adrenergic innervation in the regulation of the intrathymic T-cell maturation. For this purpose adult male DA rats were subjected to either 4-day- or 16-day-long propranolol treatment (0.40 mg propranolol/100 g/day, s.c.) and the expression of CD4/8/TCRalphabeta on thymocytes, as well as thymocyte proliferative and apoptotic index, was assessed in these animals by flow cytometric analysis. Propranolol treatment, in spite of duration, increased both the thymocyte proliferative and apoptotic index (vs. respective vehicle-treated controls). In 4-day-treated animals the thymus cellularity and thymus weight remained unaltered, while in 16-day-treated rats the values of both of these parameters were reduced (since increase in the thymocyte apoptotic index overcame that in the proliferative index). The treatments of both durations affected the thymocyte phenotypic profile in a similar pattern, but the changes were more pronounced in rats exposed to the treatment of longer duration. The relative proportion of the least mature CD4-8- double negative (DN) TCRalphabeta(-) cells was increased, those of thymocytes at distinct differentiational stages on the transitional route to the CD4+8+ double positive (DP) TCRalphabeta(low) stage decreased (all subsets of TCRalphabeta(-) in both groups of rats, and those. with low expression of TCRalphabeta in rats subjected to 16-day-long treatment) or unaltered (all subsets of TCRalphabeta(low) cells in 4-day-treated rats). Furthermore, the percentage of CD4+8+ DP TCRalphabeta(low) cells was significantly elevated, as well as those of the most mature CD4+8-TCRalphabeta(high) and CD4-8+TCRalphabeta(high) cells (the increase in the percentage of former was much more conspicuous than that of the latter), while the relative proportion of their direct detectable precursors (CD4+8+ DP TCRalphabeta(high)) Was reduced. Thus, the present study: i) further supports notion of pharmacological manipulation of adrenergic action as an efficient means in modulation of the T-cell development, and hence T-cell-dependent immune response, and ii) provides more specific insight into T-cell maturation sequence point/s particularly sensitive to beta-adrenoceptor ligand action.",
publisher = "Informa Healthcare, London",
journal = "Immunopharmacology and Immunotoxicology",
title = "Thymopoiesis following chronic blockade of beta-adrenoceptors",
volume = "25",
number = "4",
pages = "513-528",
doi = "10.1081/IPH-120026437"
}

Rauski, A., Kosec, D., Vidić-Danković, B., Radojević, K., Plećaš-Solarović, B.,& Leposavić, G.. (2003). Thymopoiesis following chronic blockade of beta-adrenoceptors. in Immunopharmacology and Immunotoxicology
Informa Healthcare, London., 25(4), 513-528.
https://doi.org/10.1081/IPH-120026437

Rauski A, Kosec D, Vidić-Danković B, Radojević K, Plećaš-Solarović B, Leposavić G. Thymopoiesis following chronic blockade of beta-adrenoceptors. in Immunopharmacology and Immunotoxicology. 2003;25(4):513-528.
doi:10.1081/IPH-120026437 .

Rauski, Aleksandra, Kosec, Duško, Vidić-Danković, Biljana, Radojević, Katarina, Plećaš-Solarović, Bosiljka, Leposavić, Gordana, "Thymopoiesis following chronic blockade of beta-adrenoceptors" in Immunopharmacology and Immunotoxicology, 25, no. 4 (2003):513-528,
https://doi.org/10.1081/IPH-120026437 . .