Interactions of Neuromodulators with Cells of the Immune System

The research program is designed to explore the effects of norepinephrine NE and other neuromodulators on non-neuronal cells. During the past year significant progress has been made in four inter-related areas 1 The effects of norepinephrine on mitogenstimulated spleen lymphocytes, thymocytes, nude mouse lymphocytes and Balbc T cell lymphosarcoma cells S49 cells has been examined in a serum-free culture system. Norepinephrine has been shown to mediate inhibition of both T B cell activation, probably through different mechanisms which may involve cyclic AMP in the T cell but not in the B cell. 2 NE also inhibits IL2 generated lymphocyte activation in serum-free culture, suggesting that the mechanisms of NE-mediated IL2 inhibition is distel to ConA binding and may also involve IL2 receptor regulation. 3 In contrast to its effects on immmune cells, NE mediates keratinocyte mitogenesis. 4 NE appears to down regulate the appearance of thyl protein on the surface of lymphocytes, thymocytes and keratinocytes. Parallel experiments with cAMP show a similar effect of cAMP-mediated thyl protein down regulation, suggesting that cAMP could be mechanistically involved with thyl gene expression.