Short exposure of maturing, bone marrow-derived dendritic cells to norepinephrine: impact on kinetics of cytokine production and Th development.
The information gathered by dendritic cells (DC) during the innate immune response to a pathogen is determinant for the type of adaptive response. Here we show that short-term (3 h) exposure of bone marrow-derived DC to norepinephrine (NE), at the beginning of lipopolysaccharide (LPS) or keyhole limpet hemocyanin (KLH) stimulation hampers IL-12 production and increases IL-10 release. The NE effect was mediated by both beta- and alpha2-adrenergic receptors. The capacity of NE-exposed DC to produce IL-12 upon CD40 cross-linking as well as to stimulate allogeneic T-helper (Th) lymphocytes was reduced. Adoptive transfer of NE-exposed DC induced a Th2 slanted response in vivo. Thus, a brief NE exposure of antigen-stimulated DC seems to limit their Th1 polarizing properties. Noteworthy, the ganglionic blocker pentolinium administered in mice before skin sensitization with fluoroscein isothiocyanate (FITC) could increase the Th1-type response in the draining lymph nodes. Our results suggest that the extent of Th differentiation in the response to an antigen might be influenced by the local sympathetic nervous activity in the early phase of dendritic cell stimulation.
Maestroni
Georges J M
GJ
Center for Experimental Pathology, Istituto Cantonale di Patologia, Via in Selva 24, P.O. Box 6601, Locarno, Switzerland. georges.maestroni@ti.ch
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology / Q000294:innervation* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D006433:Hemocyanins / Q000494:pharmacology; D007157:Immunologic Surveillance / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008771:Nordefrin / Q000378:metabolism* / Q000494:pharmacology; D017779:Sympathetic Fibers, Postganglionic / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*
D016207:Cytokines; D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D008771:Nordefrin