Dendritic cell migration controlled by alpha 1b-adrenergic receptors.
Dendritic cells (DC) bring Ags into lymphoid organs via lymphatic vessels. In this study, we investigated the possibility that the sympathetic neurotransmitter norepinephrine (NE) influences DC migration. Murine epidermal Langerhans cells mobilization is enhanced by systemic treatment with the alpha(2)-adrenergic antagonist yohimbine and inhibited by local treatment with the specific alpha(1)-adrenergic antagonist prazosin (PRA). Consistently, NE enhances spontaneous emigration of DC from ear skin explants, and PRA inhibits this effect. In addition, local treatment with PRA during sensitization with FITC inhibits the contact hypersensitivity response 6 days later. In vitro, bone marrow-derived immature, but not CD40-stimulated mature DC migrate in response to NE, and this effect is neutralized by PRA. NE seems to exert both a chemotactic and chemokinetic activity on immature DC. Coherently, immature, but not mature DC, express mRNA coding for the alpha(1b)-adrenergic receptor subtype. Inactivation of this adrenergic receptor by the specific and irreversible antagonist chloroethylclonidine hinders the migration of injected DC from the footpad to regional lymph nodes. Thus, besides regulating lymph flow, the sympathetic innervation of lymphatic vessels may participate in directing DC migration from the site of inflammation to regional lymph nodes. Alternatively, the chemokinetic activity of NE may enhance the ability of DC to sample local Ags, and hence increase the number of DC migrating to the draining lymph nodes. This finding might improve our understanding of the biological basis of skin diseases and allergic reactions, and opens new pharmacological possibilities to modulate the immune response.
Maestroni
G J
GJ
Center for Experimental Pathology, Istituto Cantonale di Patologia, Locarno, Switzerland. icpcps@guest.cscs.ch
D000279:Administration, Cutaneous; D019264:Adoptive Transfer; D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D003877:Dermatitis, Contact / Q000276:immunology; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000502:physiology; D009924:Organ Culture Techniques; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis / Q000502:physiology*; D012867:Skin / Q000166:cytology
C547717:Adra1b protein, mouse; D018340:Receptors, Adrenergic, alpha-1; D016650:Fluorescein-5-isothiocyanate; D009638:Norepinephrine