Abstract
Immunological activation of T cells enhances synthesis of acetylcholine (ACh) and transcription of choline acetyltransferase (ChAT), M 5 muscarinic ACh receptor (mAChR) and acetylcholinesterase (AChE). Stimulation of mAChRs on T and B cells causes oscillating Ca 2+-signaling and up-regulation of c-fos expression; moreover, M 1 mAChRs play a crucial role in the differentiation of CD8 + T cells into cytolytic T lymphocytes. Collectively, these findings suggest that immune cell function is regulated by its own cholinergic system. Bearing that in mind, we tested whether immune function can be regulated via mAChR-mediated pathways by immunizing combined M 1 and M 5 mAChR knockout (M 1/M 5 KO) and wild-type (WT) C57BL/6JJcl mice with ovalbumin (OVA) and measuring serum IgG 1 and IgM 1 wk later. We found that serum levels of total and anti-OVA-specific IgG 1 were significantly lower in M 1/M 5 KO than WT mice, though there was no difference in serum levels of total and anti-OVA-specific IgM between the two genotypes. Secretion of interleukin (IL)-6 from activated spleen cells was significantly reduced in M 1/M 5 KO mice, whereas there was no significant change in gamma interferon secretion. Expression of AChE mRNA was significantly reduced in activated spleen cells from M 1/M 5 KO mice. These results suggest that M 1 and/or M 5 mAChRs are involved in regulating cytokine ( e.g., IL-6) production, leading to modulation of antibody class switching from IgM to IgG 1, but are not involved in the initial generation of the antibody response. They also support the notion that a non-neuronal cholinergic system is involved in regulating immune cell function.
Published Version
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