Nicotine attenuates activation of tissue resident macrophages in the mouse stomach through the β2 nicotinic acetylcholine receptor.

<h4>Background</h4>The cholinergic anti-inflammatory pathway is an endogenous mechanism by which the autonomic nervous system attenuates macrophage activation via nicotinic acetylcholine receptors (nAChR). This concept has however not been demonstrated at a cellular level in intact tissu...

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Autores principales:	Andrea Nemethova, Klaus Michel, Pedro J Gomez-Pinilla, Guy E Boeckxstaens, Michael Schemann
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/27e8df46de444536889f055ec4bf76f5
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spelling	oai:doaj.org-article:27e8df46de444536889f055ec4bf76f52021-11-18T08:48:41ZNicotine attenuates activation of tissue resident macrophages in the mouse stomach through the β2 nicotinic acetylcholine receptor.1932-620310.1371/journal.pone.0079264https://doaj.org/article/27e8df46de444536889f055ec4bf76f52013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24223920/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The cholinergic anti-inflammatory pathway is an endogenous mechanism by which the autonomic nervous system attenuates macrophage activation via nicotinic acetylcholine receptors (nAChR). This concept has however not been demonstrated at a cellular level in intact tissue. To this end, we have studied the effect of nicotine on the activation of resident macrophages in a mouse stomach preparation by means of calcium imaging.<h4>Methods</h4>Calcium transients ([Ca(2+)]i) in resident macrophages were recorded in a mouse stomach preparation containing myenteric plexus and muscle layers by Fluo-4. Activation of macrophages was achieved by focal puff administration of ATP. The effects of nicotine on activation of macrophages were evaluated and the nAChR involved was pharmacologically characterized. The proximity of cholinergic nerves to macrophages was quantified by confocal microscopy. Expression of β2 and α7 nAChR was evaluated by β2 immunohistochemistry and fluorophore-tagged α-bungarotoxin.<h4>Results</h4>In 83% of macrophages cholinergic varicose nerve fibers were detected at distances <900 nm. The ATP induced [Ca(2+)]i increase was significantly inhibited in 65% or 55% of macrophages by 100 µM or 10 µM nicotine, respectively. This inhibitory effect was reversed by the β2 nAChR preferring antagonist dihydro-β-eryhtroidine but not by hexamethonium (non-selective nAChR-antagonist), mecamylamine (α3β4 nAChR-preferring antagonist), α-bungarotoxin or methyllycaconitine (both α7 nAChR-preferring antagonist). Macrophages in the stomach express β2 but not α7 nAChR at protein level, while those in the intestine express both receptor subunits.<h4>Conclusion</h4>This study is the first in situ demonstration of an inhibition of macrophage activation by nicotine suggesting functional signaling between cholinergic neurons and macrophages in the stomach. The data suggest that the β2 subunit of the nAChR is critically involved in the nicotine-induced inhibition of these resident macrophages.Andrea NemethovaKlaus MichelPedro J Gomez-PinillaGuy E BoeckxstaensMichael SchemannPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e79264 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andrea Nemethova Klaus Michel Pedro J Gomez-Pinilla Guy E Boeckxstaens Michael Schemann Nicotine attenuates activation of tissue resident macrophages in the mouse stomach through the β2 nicotinic acetylcholine receptor.
description	<h4>Background</h4>The cholinergic anti-inflammatory pathway is an endogenous mechanism by which the autonomic nervous system attenuates macrophage activation via nicotinic acetylcholine receptors (nAChR). This concept has however not been demonstrated at a cellular level in intact tissue. To this end, we have studied the effect of nicotine on the activation of resident macrophages in a mouse stomach preparation by means of calcium imaging.<h4>Methods</h4>Calcium transients ([Ca(2+)]i) in resident macrophages were recorded in a mouse stomach preparation containing myenteric plexus and muscle layers by Fluo-4. Activation of macrophages was achieved by focal puff administration of ATP. The effects of nicotine on activation of macrophages were evaluated and the nAChR involved was pharmacologically characterized. The proximity of cholinergic nerves to macrophages was quantified by confocal microscopy. Expression of β2 and α7 nAChR was evaluated by β2 immunohistochemistry and fluorophore-tagged α-bungarotoxin.<h4>Results</h4>In 83% of macrophages cholinergic varicose nerve fibers were detected at distances <900 nm. The ATP induced [Ca(2+)]i increase was significantly inhibited in 65% or 55% of macrophages by 100 µM or 10 µM nicotine, respectively. This inhibitory effect was reversed by the β2 nAChR preferring antagonist dihydro-β-eryhtroidine but not by hexamethonium (non-selective nAChR-antagonist), mecamylamine (α3β4 nAChR-preferring antagonist), α-bungarotoxin or methyllycaconitine (both α7 nAChR-preferring antagonist). Macrophages in the stomach express β2 but not α7 nAChR at protein level, while those in the intestine express both receptor subunits.<h4>Conclusion</h4>This study is the first in situ demonstration of an inhibition of macrophage activation by nicotine suggesting functional signaling between cholinergic neurons and macrophages in the stomach. The data suggest that the β2 subunit of the nAChR is critically involved in the nicotine-induced inhibition of these resident macrophages.
format	article
author	Andrea Nemethova Klaus Michel Pedro J Gomez-Pinilla Guy E Boeckxstaens Michael Schemann
author_facet	Andrea Nemethova Klaus Michel Pedro J Gomez-Pinilla Guy E Boeckxstaens Michael Schemann
author_sort	Andrea Nemethova
title	Nicotine attenuates activation of tissue resident macrophages in the mouse stomach through the β2 nicotinic acetylcholine receptor.
title_short	Nicotine attenuates activation of tissue resident macrophages in the mouse stomach through the β2 nicotinic acetylcholine receptor.
title_full	Nicotine attenuates activation of tissue resident macrophages in the mouse stomach through the β2 nicotinic acetylcholine receptor.
title_fullStr	Nicotine attenuates activation of tissue resident macrophages in the mouse stomach through the β2 nicotinic acetylcholine receptor.
title_full_unstemmed	Nicotine attenuates activation of tissue resident macrophages in the mouse stomach through the β2 nicotinic acetylcholine receptor.
title_sort	nicotine attenuates activation of tissue resident macrophages in the mouse stomach through the β2 nicotinic acetylcholine receptor.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/27e8df46de444536889f055ec4bf76f5
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Nicotine attenuates activation of tissue resident macrophages in the mouse stomach through the β2 nicotinic acetylcholine receptor.

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