Effects of catecholamines on thymocyte apoptosis and proliferation depend on thymocyte microenvironment

• Catecholamine (CA) synthesis in adult thymus organ (ATOC) and thymocyte culture.
• CAs affect thymocyte apoptosis/proliferation in a subset-specific manner. Propranolol exerts opposing effects on thymocytes in ATOC and cell culture.
• β-adrenoceptor (AR)-mediated effects on thymocytes depend on the microenvironment.
• CAs exert opposing effects on thymocyte apoptosis/proliferation via a-α- and β-ARs.

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 CD3high 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.