LYMPHOCYTE-MEDIATED REGULATION OF NEUROTRANSMITTER GENE-EXPRESSION IN RAT SYMPATHETIC-GANGLIA

It has been previously shown that sympathetic noradrenergic nerve fibers, in addition to supplying the smooth muscle of the splenic capsule, trabeculae and blood vessels, also form very tight appositions with lymphocytes of the periarteriolar lymphatic sheath. To determine whether there is a direct communication between the sympathetic neurons and the immune cells we have grown dissociated superior cervical ganglion (SCG) neurons together with splenic lymphocytes. Sympathetic neurons were grown both as mixed preparations (neurons and non-neuronal ganglion cells) and neuron-enriched preparations. These systems were used to investigate whether coculture with splenocytes alters neurotransmitter gene expression in SCG cultures. Northern blot analysis was used to measure changes in neurotransmitter mRNA expression. The results showed that expression of mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, was significantly decreased when SCG cultures were grown in the presence of spleen cells compared to control SCGs grown either alone or in the presence of erythrocytes. When the mitogen concanavalin A (ConA) was used to stimulate the spleen cells in the cocultures the decrease in TH was more pronounced. In contrast, preprotachykinin-A (PPT-A) mRNA expression in cultured SCGs increased in the cocultures. Another neuropeptide, neuropeptide Y (NPY), showed different responses in the presence of stimulated vs. unstimulated splenocytes. NPY mRNA was slightly increased in the presence of resting spleen cells, but showed a 70% decrease when ConA was added to the cocultures. Thus, our results suggest that lymphocytes can differentially regulate neurotransmitter gene expression in sympathetic ganglia.