Enhanced Dendritic Cell Antigen Uptake via α2 Adrenoceptor-Mediated PI3K Activation Following Brief Exposure to Noradrenaline

Although noradrenaline (NA), a stress-associated neurotransmitter, seems to affect the immune system, the precise mechanisms underlying NA-mediated immunoregulation are not fully understood. We examined the effect of NA on Ag uptake (endocytosis) by dendritic cells (DCs) using murine bone marrow-derived DCs and fluorescence-labeled endocytic tracers (dextran and OVA). Ag uptake by DCs notably increased following a very brief treatment (3 min) with NA. NA-induced endocytosis was completely blocked by treatment with alpha(2)-adrenoceptor antagonist yohimbine. Neither alpha(1)-adrenoceptor antagonist prazosin nor beta-adrenoceptor antagonist propranolol affected NA-induced endocytosis by DCs. A selective a2-adrenoceptor agonist, azepexole (B-HT 933), also significantly increased endocytosis by DCs. Thus, the alpha(2)-adrenoceptor seems to be responsible for NA-induced DC endocytosis. In parallel, NA markedly activated intracellular signaling pathways of PI3K and ERK1/2 in DCs. NA-mediated activation of these pathways was completely inhibited by yohimbine treatment. Blocking PI3K activation significantly reduced NA-induced endocytosis by DCs. Based on these results, NA rapidly enhances Ag capture by DCs via alpha(2) adrenoceptor-mediated PI3K activation, which may be associated with immune enhancement following acute stress. The Journal of Immunology, 2010, 185: 5762-5768.