Decreased catecholamine-induced cell death in B lymphocytes from patients with rheumatoid arthritis.
The expression of beta2-adrenergic receptors (beta2-R) on B lymphocytes and agonist-induced cAMP production is reduced in patients with rheumatoid arthritis (RA). To further study functional consequences of the diminished beta2-R density on B lymphocytes in RA patients, agonist-induced cell death was evaluated and compared to healthy controls. B lymphocytes from patients with RA and healthy controls were activated with anti-IgM-antibody. Coincubation was carried out with isoprenaline (iso, 0.001-10 microM). Apoptotic and necrotic cells were determined using Annexin-V and propidium-iodide staining. beta2-R-induced cell death in B cells from healthy volunteers was stimulated after 24 h (medium, 21.2 +/- 1.6%; iso, 34.6 +/- 4.4%; increase 59.3 +/- 10.1%). However, in RA patients the increase in cell death following beta2-R stimulation (21.8 +/- 8.9%) was significantly impaired (p = 0.02). Our data demonstrate that catecholamine-induced cell death after stimulation of beta2-R on B lymphocytes is decreased in RA patients, possibly contributing to the pathogenesis of the disease.
University Hospital Leipzig, Department of Medicine IV, Leipzig, Germany. wahm@medizin.uni-leipzig.de
M
M
Wahle
M
M
Pierer
A
A
Krause
S
S
Kolker
C G O
CG
Baerwald
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D017304:Annexin A5 / Q000032:analysis; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology*; D001402:B-Lymphocytes / Q000473:pathology*; D015415:Biomarkers; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D002478:Cells, Cultured / Q000187:drug effects; D004351:Drug Resistance; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects; D013726:Terbutaline / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D017304:Annexin A5; D000888:Antibodies, Anti-Idiotypic; D015415:Biomarkers; D018343:Receptors, Adrenergic, beta-2; C044203:anti-IgM; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D007545:Isoproterenol; D013726:Terbutaline; D004837:Epinephrine