Enhanced dendritic cell antigen uptake via alpha2 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 α(2)-adrenoceptor antagonist yohimbine. Neither α(1)-adrenoceptor antagonist prazosin nor β-adrenoceptor antagonist propranolol affected NA-induced endocytosis by DCs. A selective α(2)-adrenoceptor agonist, azepexole (B-HT 933), also significantly increased endocytosis by DCs. Thus, the α(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 α(2) adrenoceptor-mediated PI3K activation, which may be associated with immune enhancement following acute stress.