Beta 2-adrenergic stimulation causes detachment of natural killer cells from cultured endothelium.
Physical exercise, mental stress, or infusion of beta-adrenergic agonists result in an increase in the number of natural killer (NK) cells in the peripheral circulation. In view of the specific migration pattern of NK cells in vivo, it has been suggested that these cells may be released from the marginating pool in blood vessels. In the present report, the in vitro effect of catecholamines on the adhesion of NK cells to unstimulated human endothelial cells (EC) was characterized. Peripheral blood mononuclear cells were allowed to adhere to monolayers of EC, after which the adherent lymphocyte fraction was analyzed phenotypically by flow cytometry. NK cells were found to adhere preferentially to EC, a process that was reversed by the addition of various adrenergic 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 was concentration-dependent, with an ED50 of 2 x 10(-10)M. Using a panel of alpha- and beta-adrenergic agonists and antagonists, we show that the detachment of NK cells is mediated via beta 2-adrenergic receptors. In line with the lower affinity for beta 2-adrenergic receptors, norepinephrine was less effective than EPI in inducing detachment of NK cells from EC. Direct activation of adenylate-cyclase with forskolin gave similar results as observed with EPI, indicating that signaling through cAMP is necessary to induce detachment of NK cells from EC. The results of the present study lend support to the hypothesis that catecholamines, via beta 2-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.
Benschop
R J
RJ
Department of Immunology, University Hospital, The Netherlands.
Oostveen
F G
FG
Heijnen
C J
CJ
Ballieux
R E
RE
D000262:Adenylyl Cyclases / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*
D018343:Receptors, Adrenergic, beta-2; D000262:Adenylyl Cyclases; D004837:Epinephrine