THE EFFECTS OF BETA-ADRENOCEPTOR STIMULATION ON ADHESION OF HUMAN NATURAL-KILLER-CELLS TO CULTURED ENDOTHELIUM

1 The circulation of natural killer (NK) cells in vivo is influenced b y physical exercise, mental stress, and infusion of beta-adrenoceptor agonists. We have previously presented in vitro data, showing that bet a(2)-adrenoceptor agonists induce detachment of NK cells from endothel ial cells (EC), supporting the hypothesis that NK cells can be recruit ed from the marginating pool in blood vessels. 2 Because NK cells as w ell as EC express beta(2)-adrenoceptors, the present study was conduct ed to investigate whether stimulation of the beta-adrenoceptors on NK cells, EC or both cell types is required to induce detachment from EC. 3 Cells were pretreated (15 min) with a selective B-2-adrenoceptor an tagonist, GR81706, at various concentrations. The duration of beta-adr enoceptor blockade was tested by determining the adenosine 3',5'-cycli c monophosphate (cyclic AMP) production induced by terbutaline (a beta (2)-adrenoceptor specific agonist). This receptor-mediated response wa s effectively inhibited for at least 4 h, whereas the cyclic AMP produ ction in response to forskolin (a direct activator of adenylate-cyclas e) was not affected. 4 Functional adhesion assays were then performed to determine the role of beta-adrenoceptors on the different cell type s involved (NK and EC) in catecholamine-induced detachment. Peripheral blood mononuclear cells were allowed to adhere for 1 h to monolayers of unstimulated EC in the presence or absence of cyclic AMP inducing a gents, and the percentage of NK cells in the adhering lymphocyte fract ion was determined by flow cytometry. 5 Both adrenaline (10(-5) M) and forskolin (10(-5) M) caused detachment of NK cells from EC. After blo ckade of the beta(2)-adrenoceptors on NK cells by pretreatment with GR 81706 (10(-6) M), the effect of adrenaline on NK cells adhesion was pr etented; after blockade of the beta(2)-adrenoceptors on EC, NK cell ad hesion was still significantly reduced by adrenaline. In all cases, fo rskolin caused detachment of NK cells. 6 To establish further that sti mulation of beta-adrenoceptors on NK cells is sufficient to cause deta chment, we showed that adrenaline also reduced adhesion of NK cells to monolayers of Chinese hamster ovary cells, which do not express beta- adrenoceptors. 7 Together, these results show that stimulation of beta (2)-adrenoceptors on NK cells negatively influences their capacity to adhere to EC, and that beta(2)-adrenoceptors on EC playa negligible ro le in this phenomenon.