SLURP-1, an endogenous alpha7 nAChR allosteric ligand, expression in human immune organs and function in regulation of lymphocytic cholinergic activity

      T cells have the ability to synthesize acetylcholine (ACh) by choline acetyltransferase (ChAT). Various subtypes of nicotinic ACh receptors (nAChRs) including alpha7 nAChRs are expressed in immune cells, such as lymphocytes, macrophages (Mϕ), and dendritic cells (DC). Furthermore, gene expression for SLURP-1, an endogenous alpha7 nAChR allosteric ligand, has been detected in various tissues including skin, lung and immune organs. Recent studies have suggested the involvement of alpha7 nAChRs in T cell differentiation and the necessity of SLURP-1 for normal T cell activation. In order to investigate the role played by SLURP-1 in T cell activation, focusing on α7 nAChRs, we examined immunohistochemical SLURP-1expression in human spleen, lymph node and tonsil, and effects of SLURP-1 on cell growth and ACh synthesis in human leukemic T cell line MOLT-3, as a model of T cell. DC-like–shaped SLURP-1-positive cells were detected in the tonsil, locating mainly in the marginal zone between crypt and lymphoid follicle. However, SLURP-1-positive cells did not show any reactivity with the antibodies against the markers of T and B cells, DCs, Mϕ, monocytes, and mast cells. Stimulation of MOLT-3 cells with phytohemagglutinine (PHA), a T cell activator, suppressed cell growth and increased the intracelluar ACh content. These effects of PHA were abolished by methyllycaconitine (MLA, 100 nM), a specific antagonist for alpha7 nAChR, suggesting PHA activates T cells via alpha7 nAChR-mediated pathways. SLURP-1 (0.5 μg/ml) suppressed the cell growth, and increased the intracellular ACh content and ChAT gene expression in the MOLT-3. MLA reversed these effects elicited by SLURP-1. The results demonstrate that SLURP-1 stimulates lymphocytic cholinergic activity via alpha7 nAChR-mediated pathways in T cells. Taken together, these findings suggest the possible involvement of SLURP-1 in regulation of T cell differentiation during immunological activation, by facilitating lymphocytic cholinergic activity via alpha7 nAChR-mediated pathways.
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