Norepinephrine and serotonin content of the murine spleen: its relationship to lymphocyte beta-adrenergic receptor density and the humoral immune response in vivo and in vitro

Numerous reports in the literature describe the effects of beta-adrenergic agonists and/or their second messenger cyclic AMP on in vitro and in vivo immune responses. The fact that the murine spleen receives rich adrenergic innervation and that the pharmacologic disruption of this innervation leads to altered immune responsiveness has led some investigators to postulate that the immune system may be modulated in vivo by the sympathetic nervous system. In this report HPLC is used to quantitate the norepinephrine (NE) and serotonin (5-HT) found in the B6C3F1 spleen. These transmitters were found to be distributed nonhomogeneously among the cell, supernatant, and capsule fractions of the spleen. The majority of NE was found in the capsule while most 5-HT was found associated with the cell pellet. During an immune response to sheep red blood cells the concentration of NE in the spleen was found to be decreased. However, the total amount of splenic NE was unaltered and thus the decreased concentration may be attributed to the increased weight of immunized spleens. Simultaneously, the total amount of the dopamine metabolite 3,4-dihydroxyphenylacetic acid found in the spleen was found to be increased, a difference not explained by increased spleen size. These results suggest an antigen-induced increase in sympathetic activity in the spleen. Splenic NE could be rapidly depleted using 6-hydroxydopamine. Lymphocytes from the NE-depleted animals were found to have upregulated the number of beta-adrenergic receptors on their surfaces and demonstrated a reduced ability to respond to sheep red blood cells in vitro.