ADRENERGIC REGULATION OF LYMPHOCYTE PROLIFERATION

RUBINSTEIN R; SGANGA L; BARREIRO-ARCOS ML; CREMASCHI G; WALD M

Mar del Plata, Buenos Aires, Argentina

Congreso; XXXVII Reunión Anual de la SAFE; 2005

Sociedad Argentina de Farmacología Experimental

An important physiological mechanism that influences immune regulation involves the sympathetic nervous system. The predominant and more studied adrenergic (A) receptor on T and B cells is the b2-A, however little is known about the a-A stimulation.  In this study we examined the effect of a-A agonism on the regulation of lymphocyte activation.  Lymph node or spleen cells from BALB/c mice were stimulated by mitogens and lymphocyte activation was monitored by measuring 3H-thymidine incorporation. The a2-A agonist, clonidine, stimulated the activation both, lymph cells by concanavalin A – a T-cell specific mitogen - and spleen cells by LPS – a T independent B-cell mitogen-. The a1-A agonist, cirazoline, did not stimulate lymphocyte activation.  The natural agonist, noradrenaline (NA), shows a biphasic effect on T cell proliferation, stimulating and inhibiting at low and high concentrations respectively.  NA also stimulates B cell proliferation.  When determining the specificity of signal transduction pathway, a2-A stimulation did not inhibit adenylyl cyclase activity but results in the activation of protein kinase C (PKC).  Using RT-PCR techniche, we investigated the expression of a2-A receptor subtypes. A fragment of the a2 B A receptor was amplified in T and B cells. This finding describes that a2-A agonists are able to modulate lymphocyte proliferation through a2 B-A adrenergic receptor mediated activation of PKC.