Catecholamine production and tyrosine hydroxylase expression in peripheral blood mononuclear cells from multiple sclerosis patients: effect of cell stimulation and possible relevance for activation-induced apoptosis.
Sympathoadrenergic mechanisms may play a role in multiple sclerosis (MS). We examined catecholamine (CA) levels and production and tyrosine hydroxylase (TH) expression in peripheral blood mononuclear cells (PBMCs) from MS patients, and the correlation between CA production and apoptosis in PBMCs. PBMCs from MS patients had increased norepinephrine (NE) levels. However, phytohaemagglutinin (PHA)-stimulated PBMCs from MS patients with active disease synthesized less dopamine (DA) than cells from both healthy controls and patients with inactive disease. PBMCs from patients with inactive disease showed lower expression of TH. Pharmacological inhibition of TH in cultured PBMCs stimulated with PHA reduced the percentage of apoptotic cells. Since a failure of activation-induced apoptosis in immune cells may be involved in MS, it is suggested that altered CA production by PBMCs may be implicated in such dysregulation.
Cosentino
Marco
M
Center for Research in Clinical and Applied Pharmacology, University of Insubria, Varese, Italy. marco.cosentino@uninsubria.it
Zaffaroni
Mauro
M
Marino
Franca
F
Bombelli
Raffaella
R
Ferrari
Marco
M
Rasini
Emanuela
E
Lecchini
Sergio
S
Ghezzi
Angelo
A
Frigo
Gianmario
G
D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D002395:Catecholamines / Q000096:biosynthesis* / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000201:enzymology / Q000276:immunology*; D015213:Neuroimmunomodulation / Q000276:immunology; D013564:Sympathetic Nervous System / Q000276:immunology; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019805:alpha-Methyltyrosine / Q000494:pharmacology
D002395:Catecholamines; D004791:Enzyme Inhibitors; D019805:alpha-Methyltyrosine; D014446:Tyrosine 3-Monooxygenase