Sympathetic abnormalities during autoimmune processes: potential relevance of noradrenaline-induced apoptosis.
The sympathetic nervous system is one of the major pathways involved in immune-neuroendocrine interactions. Disturbances in these interactions are likely to have consequences during lymphoproliferative diseases. Work derived from our group as well as from several others led us to the hypothesis that the overstimulation of the immune system that characterizes this type of pathology results in decreased sympathetic nerve activity in lymphoid organs. To explore this possibility, we used as a model lpr/lpr mice, which develop a genetically determined autoimmune, lupus-like lymphoproliferative disease. We show that 18-week-old female C57Bl/6J lpr/lpr mice, which do not show overt symptoms of the disease but already have increased IgM and IgG2a levels in the blood, have decreased noradrenaline (NA) concentration and content in the spleen, but not in the kidney, as compared to normal C57Bl/6J littermates. Lpr/lpr mice do not express normal Fas, and therefore apoptosis cannot be triggered through this receptor. The defects in sympathetic innervation in the spleen of lpr/lpr mice prompted us to evaluate whether NA could influence lymphoid cell mass by inducing apoptosis. We found that NA can directly induce apoptosis in normal lymphoid cells via beta-adrenergic receptors. From the reported results we propose that reduction in sympathetic nerve function in lpr/lpr mice contributes to aggravation of the disease and suggest that in addition to the incapacity to mount Fas-mediated apoptosis, a second proapoptotic mechanism, namely, that triggered by NA, is defective in these animals because of reduced availability of the neurotransmitter.
Del Rey
Adriana
A
Department of Immunophysiology, Institute of Physiology, Medical Faculty, 35037, Marburg, Germany. delray@mailer.uni-marburg.de
Kabiersch
Alexa
A
Petzoldt
Sigrid
S
Besedovsky
Hugo O
HO
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D005260:Female; D008214:Lymphocytes / Q000166:cytology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D013154:Spleen / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D009638:Norepinephrine