BETA(2)-ADRENERGIC STIMULATION CAUSES DETACHMENT OF NATURAL-KILLER-CELLS FROM CULTURED ENDOTHELIUM

Physical exercise, mental stress, or infusion of beta-adrenergic agoni sts result in an increase in the number of natural killer (NK) cells i n the peripheral circulation. In view of the specific migration patter n of NK cells in vivo, it has been suggested that these cells may be r eleased from the marginating pool in blood vessels. In the present rep ort, the in vitro effect of catecholamines on the adhesion of NK cells to unstimulated human endothelial cells (EC) was characterized. Perip heral blood mononuclear cells were allowed to adhere to monolayers of EC, after which the adherent lymphocyte fraction was analyzed phenotyp ically by flow cytometry. NK cells were found to adhere preferentially to EC, a process that was reversed by the addition of various adrener gic agonists. Catecholamines selectively affected adhesion of NK cells and had no effect on T cell adhesion to EC, as was determined by the use of purified cell populations. Detachment of NK cells from EC could be achieved by short incubations (5 min) with epinephrine (EPI) and w as concentration-dependent, with an ED50 of 2 X 10(-10) M. Using a pan el of alpha- and beta-adrenergic agonists and antagonists, we show tha t the detachment of NK cells is mediated via beta2-adrenergic receptor s. In line with the lower affinity for beta2-adrenergic receptors, nor epinephrine was less effective than EPI in inducing detachment of NK c ells from EC. Direct activation of adenylate-cyclase with forskolin ga ve similar results as observed with EPI, indicating that signaling thr ough cAMP is necessary to induce detachment of NK cells from EC. The r esults of the present study lend support to the hypothesis that catech olamines, via beta2-adrenergic receptors, can induce recruitment of NK cells from the marginating pool to the circulating pool, by changing the adhesive interactions between NK cells and EC.