Effects of catecholamines on thymocyte apoptosis and proliferation depend on thymocyte microenvironment.
The present study, through quantification of tyrosine hydroxylase (TH) expression and catecholamine (CA) content in the presence and in the absence of α-methyl-p-tyrosine (AMPT), a TH inhibitor, in adult thymic organ (ATOC) and thymocyte culture, demonstrated that thymic cells produce CAs. In addition, in ATOC an increase in β2-adrenoceptor (AR) mRNA expression and β2-AR thymocyte surface density was registered. Furthermore, AMPT (10(-4)M), as propranolol (10(-4)M), augmented thymocyte apoptosis and diminished thymocyte proliferation in ATOC. Propranolol exerted these effects acting on CD3(high) thymocytes. However, in thymocyte cultures, propranolol (10(-6)M) acting on the same thymocyte subset exerted the opposing effect on thymocyte apoptosis and ConA-stimulated proliferation. This suggested that, depending on thymocyte microenvironment, differential effects can be induced through the same type of AR. Additionally, arterenol (10(-8) to 10(-6)M), similar to propranolol, diminished apoptosis, but increased ConA-stimulated thymocyte proliferation in thymocyte culture. However, differently from propranolol, arterenol affected manly CD3- thymocyte subset, which harbors majority of α1-AR+thymocytes. Additionally, arterenol showed a dose-dependent decrease in efficiency of thymocyte apoptosis and proliferation modulation with the rise in its concentration. Considering greater affinity of arterenol for α1-ARs than for β2-ARs, the previous findings could be attributable to increased engagement of β2-ARs with the rise of arterenol concentration. Consistently, in the presence of propranolol (10(-6)M), a β-AR blocker, the arterenol (10(-8)M) effects on thymocytes were augmented. In conclusion, thymic endogenous CAs, acting through distinct AR types and, possible, the same AR type (but in different cell microenvironment) may exert the opposing effects on thymocyte apoptosis/proliferation.
Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", 458 Vojvode Stepe, 11221 Belgrade, Serbia.
Katarina
K
Radojević
Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", 458 Vojvode Stepe, 11221 Belgrade, Serbia.
Ana
A
Rakin
Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", 458 Vojvode Stepe, 11221 Belgrade, Serbia.
Ivan
I
Pilipović
Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", 458 Vojvode Stepe, 11221 Belgrade, Serbia.
Duško
D
Kosec
Department of Physiology, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe, 11221 Belgrade, Serbia.
Jasmina
J
Djikić
Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe, 11221 Belgrade, Serbia.
Biljana
B
Bufan
Immunology Research Centre "Branislav Janković", Institute of Virology, Vaccines and Sera "Torlak", 458 Vojvode Stepe, 11221 Belgrade, Serbia.
Ivana
I
Vujnović
Department of Physiology, Faculty of Pharmacy, University of Belgrade, 450 Vojvode Stepe, 11221 Belgrade, Serbia. Electronic address: Gordana.Leposavic@pharmacy.bg.ac.rs.
Gordana
G
Leposavić
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002395:Catecholamines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D009924:Organ Culture Techniques; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D060168:Thymocytes / Q000187:drug effects / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D004791:Enzyme Inhibitors; D019805:alpha-Methyltyrosine; D011433:Propranolol; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine
Adult thymus organ culture; Arterenol; Propranolol; Thymocyte apoptosis; Thymocyte culture; Thymocyte proliferation