Neurotransmitters of the sympathetic nerve terminal are powerful chemoattractants for monocytes

Macrophages in lymphoid organs are in close contact to nerve terminals of t he sympathetic nervous system. Hence, these cells could be targets of neuro nal modulation. We studied sympathetic neurotransmitters as chemoattractant s enabling the aggregation of macrophages and nerve terminals, Norepinephri ne (NE), neuropeptide Y (NPY), isoproterenol (beta-adrenergic), p-aminoclon idine (alpha(2)-adrenergic), methoxamine (alpha(1)-adrenergic), and adenosi ne triphosphate (ATP) were used to study human monocyte and macrophage migr ation in 48-well Boyden chambers, NE stimulated chemotaxis of monocytes and macrophages at an optimal concentration of 10(-10) M (P < 0.025), Isoprote renol, but not p-aminoclonidine or methoxamine, induced chemotaxis of monoc ytes (10(-10) M, P < 0.05). In these studies, elevation of cAMP is a critic al step in NE-induced chemotaxis of monocytes, NPY (10(-11) M, P < 0.05) st imulated monocyte chemotaxis as well, ATP at 10(-4) and 10(-5) M stimulated undirected cell mobility (P < 0.05), All tested neurotransmitters of the s ympathetic nerve terminal were potent chemoattractants. These findings may explain the close association of nerves and macrophages in tissue and lymph oid organs and may thus be of functional relevance in neuroimmunomodulation .