Increased high affinity beta-adrenergic receptor densities and cyclic AMP responses of CD8 cells in multiple sclerosis.
Beta-adrenergic receptor (beta R) density is increased on suppressor T-cells (Ts) from patients with chronic progressive multiple sclerosis (CPMS). We investigated the contribution of high-affinity (kh) beta R to cAMP responses of nongranular leukocyte subsets from CPMS patients and normal individuals (NL). CD8 beta R density was 1930 receptors/cell in CPMS compared to only 1020 receptors/cell in NL (t(18) = 2.73, P < 0.02). beta R densities on monocytes, B cells, and CD4 cells did not differ between groups. The increased density of beta R on CD8 cells in CPMS was entirely the result of an increase in the number of high affinity receptors. Basal level of cAMP in CD8 lymphocytes were 7.8 pmol/10(6) cells in CPMS and 3.5 pmol/10(6) cells in NL. Isoproterenol stimulation elevated cAMP levels in CD8 cells to 49.9 pmol/10(6) cells in CPMS patients and to 25.7 pmol/10(6) cells in NL (difference after activation: t(18) = 3.23, P < 0.005). No differences between groups were found in cAMP levels of other cell subsets. We also measured circulating catecholamine levels. Supine and standing epinephrine levels were not different between CPMS and NL. Supine norepinephrine (NE) levels were higher in CPMS (411 pg/ml) than in NL (268 pg/ml) (P < 0.03); upon standing, significant increases in NE occurred in both groups to 573 pg/ml in CPMS and to 494 pg/ml in NL. These results extend our previous findings of peripheral sympathetic dysregulation in CPMS and suggest a means whereby Ts function, hypothesized to play a role in the immune pathogenesis of CPMS, may be altered.
Karaszewski
J W
JW
Department of Neurology, University of Chicago, IL 60637.
Reder
A T
AT
Anlar
B
B
Arnason
G W
GW
D000328:Adult; D016827:CD8 Antigens / Q000032:analysis*; D002908:Chronic Disease; D000242:Cyclic AMP / Q000378:metabolism*; D004837:Epinephrine / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D009638:Norepinephrine / Q000097:blood; D011943:Receptors, Adrenergic, beta / Q000032:analysis*; D013564:Sympathetic Nervous System / Q000503:physiopathology; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
D016827:CD8 Antigens; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D009638:Norepinephrine; D004837:Epinephrine