CATECHOLAMINES MODULATE HUMAN NK CELL CIRCULATION AND FUNCTION VIA SPLEEN-INDEPENDENT BETA(2)-ADRENERGIC MECHANISMS

Increases in catecholamines have been shown to induce changes in migra tion of lymphocytes, in particular NK cells. To analyze the mechanisms of catecholamine-induced NK cell trafficking, normal healthy male hum an subjects and splenectomized individuals were infused with either ad renaline (0.10 mu g/kg/min), noradrenaline (0.15 mu g/kg/min), or NaCl i.v. for 20 min. Lymphocyte subsets (CD3(+), CD4(+), CD8(+)) transien tly increased after administration of both catecholamines, with most p ronounced increases (up to 600%) in NK cell numbers (CD16(+) or CD56()) after infusion of adrenaline. These changes in NK cell numbers and function were accompanied neither by alterations in expression of adhe sion molecules (CD11a, CD11b, CD31, CD43, CD44, CD62L) on NK cells nor by changes in plasma concentrations of soluble (s) adhesion molecules (sVCAM-1, sICAM-1, sE-selectin). Comparable increases in lymphocyte s ubsets were observed in splenectomized subjects, suggesting lymphocyte recruitment from other sources than the spleen. Furthermore, catechol amine-induced increases in lymphocyte subsets could be inhibited by pr etreatment with the nonselective beta-adrenoceptor antagonist proprano lol, but not by the beta(1)-selective antagonist bisoprolol. These dat a demonstrate that adrenaline and noradrenaline modulate the migratory capacity of human NK cells via spleen-independent beta(2)-adrenocepto r mechanisms.