Prolonged alpha-adrenergic stimulation causes changes in leukocyte distribution and lymphocyte apoptosis in the rat

We have previously shown in the rat model that acutely or chronically incre ased peripheral catecholamines lead to suppression of lymphocyte responsive ness via alpha 2-adrenoceptor activation. Here we investigated the effects of alpha-adrenergic treatment on total leukocyte numbers and proportions of leukocyte subsets in peripheral blood and lymphoid tissues. It was found t hat a 12-h treatment with subcutaneously implanted tablets, one containing norepinephrine (NE) and one propranolol, leads to an increase in total bloo d leukocyte counts, due to a pronounced increase in granulocytes. In contra st, the numbers of all classes of lymphocytes other than NK cells were decr eased. This decrease in blood lymphocytes is apparently not due to redistri bution, since in the thymus, spleen, mesenteric and peripheral lymph nodes, the total numbers of lymphocytes were decreased as well, without any chang es in subpopulations. Analogous results were obtained with rats adrenalecto mized before the catecholamine treatment. Animals that received the alpha-a drenergic treatment displayed significantly more apoptotic cells in the lym phoid organs, as determined by the TUNEL technique. In the spleen, the enha nced rate of apoptosis was confined to the white pulp; red pulp areas exhib ited significantly fewer apoptotic cells. Thus, an increased alpha-adrenerg ic tone in rats led to a general loss of lymphocytes due to lymphocyte dire cted apoptosis that was independent of glucocorticoids. (C) 2001 Elsevier S cience BN. All rights reserved.