Catecholamines increase lymphocyte beta 2-adrenergic receptors via a beta 2-adrenergic, spleen-dependent process.
We investigated the mechanisms underlying the increase in mononuclear leukocyte (MNL) beta 2-adrenergic receptor (AR) number and responsiveness after acute infusion of catecholamines. Infusion of isoproterenol and epinephrine, but not of norepinephrine, acutely increased MNL beta-AR density, and this was blocked by the beta 2-selective antagonist ICI 118,551 but not by the beta 1-selective antagonist bisoprolol, suggesting a beta 2-AR-mediated effect. Infusion of isoproterenol but not of norepinephrine also induced a lymphocytosis, with an increase in the number of circulating suppressor/cytolytic T (Ts/c)- and natural killer (NK)-cells but a decrease in helper T (Th)-cells, leading to a decreased Th-Ts/c-cell ratio. beta-AR density was higher in Ts/c-cells than in Th-cells. After isoproterenol infusion, beta-AR density was elevated in all lymphocyte subsets but not in monocytes or platelets, suggesting a lymphocyte-specific phenomenon. Infusion of isoproterenol in splenectomized patients did not alter lymphocyte subset composition and only slightly increased beta 2-AR density. In healthy subjects lymphocyte proliferation in response to various mitogens was attenuated after infusion of isoproterenol but not of norepinephrine; this effect was abolished in splenectomized patients. We conclude that the elevated MNL beta-AR density after acute exposure to beta-adrenergic agonists is caused by a release of lymphocyte subsets from the spleen into the circulation and/or by an exchange of lymphocyte subsets between the spleen and the circulation, whereby freshly released splenic lymphocytes appear to carry more beta-AR than those found in the circulation. This appears to impair immune responsiveness in a dual manner, by decreasing the Th-/Ts/c-cell ratio and by rendering lymphocytes more sensitive to the antiproliferative effects of catecholamines via a higher beta-AR density.
Van Tits
L J
LJ
Department of Pharmacology, University of California, San Diego, La Jolla 92093.
Michel
M C
MC
Grosse-Wilde
H
H
Happel
M
M
Eigler
F W
FW
Soliman
A
A
Brodde
O E
OE
D000328:Adult; D001792:Blood Platelets / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D013154:Spleen / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine