Diminished antigen-specific IgG1 and interleukin-6 production and acetylcholinesterase expression in combined M1 and M5 muscarinic acetylcholine receptor knockout mice.
Immunological activation of T cells enhances synthesis of acetylcholine (ACh) and transcription of choline acetyltransferase (ChAT), M5 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, M1 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 M1 and M5 mAChR knockout (M1/M5 KO) and wild-type (WT) C57BL/6JJcl mice with ovalbumin (OVA) and measuring serum IgG1 and IgM 1 wk later. We found that serum levels of total and anti-OVA-specific IgG1 were significantly lower in M1/M5 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 M1/M5 KO mice, whereas there was no significant change in gamma interferon secretion. Expression of AChE mRNA was significantly reduced in activated spleen cells from M1/M5 KO mice. These results suggest that M1 and/or M5 mAChRs are involved in regulating cytokine (e.g., IL-6) production, leading to modulation of antibody class switching from IgM to IgG1, 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.
Fujii
Yoshihito X
YX
Department of Pharmacology, Kyoritsu College of Pharmacy, Shibakoen, Minato-ku, Tokyo, Japan.
Tashiro
Ayako
A
Arimoto
Kumiko
K
Fujigaya
Hirofumi
H
Moriwaki
Yasuhiro
Y
Misawa
Hidemi
H
Fujii
Takeshi
T
Matsui
Minoru
M
Kasahara
Tadashi
T
Kawashima
Koichiro
K
D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D007074:Immunoglobulin G / Q000097:blood*; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D043643:Receptor, Muscarinic M1 / Q000172:deficiency*; D043642:Receptor, Muscarinic M5 / Q000172:deficiency*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D007074:Immunoglobulin G; D015850:Interleukin-6; D012333:RNA, Messenger; D043643:Receptor, Muscarinic M1; D043642:Receptor, Muscarinic M5; D007371:Interferon-gamma; D010047:Ovalbumin; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase