Imperial College London
Alternate

RESEARCH TECHNICIAN

Faculty of Medicine, National Heart & Lung Institute

Research Technician
 
 
 
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Contact

 

+44 (0)20 7594 7897p.fenwick

 
 
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Location

 

Technician Room 229BGuy Scadding BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Koarai:2012:10.1183/09031936.00136710,
author = {Koarai, A and Traves, SL and Fenwick, PS and Brown, SM and Chana, KK and Russell, RE and Nicholson, AG and Barnes, PJ and Donnelly, LE},
doi = {10.1183/09031936.00136710},
journal = {Eur Respir J},
pages = {698--704},
title = {Expression of muscarinic receptors by human macrophages.},
url = {http://dx.doi.org/10.1183/09031936.00136710},
volume = {39},
year = {2012}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Macrophages increase in number and are highly activated in chronic obstructive pulmonary disease (COPD). Muscarinic receptor antagonists inhibit acetylcholine-stimulated release of neutrophilic chemoattractants, suggesting that acetylcholine may regulate macrophage responses. Therefore, expression and function of components of the non-neuronal cholinergic system in monocyte-macrophage cells was investigated. RNA was isolated from monocytes, monocyte-derived macrophages (MDMs), lung and alveolar macrophages from nonsmokers, smokers and COPD patients, and expression of the high-affinity choline transporter, choline acetyltransferase, vesicular acetylcholine transporter and muscarinic receptors (M(1)-M(5)) ascertained using real-time PCR. M(2) and M(3) receptor expression was confirmed using immunocytochemistry. Release of interleukin (IL)-8, IL-6 and leukotriene (LT)B(4) were measured by ELISA or EIA. All monocyte-macrophage cells expressed mRNA for components of the non-neuronal cholinergic system. Lung macrophages expressed significantly more M(1) mRNA compared with monocytes, and both lung macrophages and alveolar macrophages expressed the highest levels of M(3) mRNA. Expression of M(2) and M(3) protein was confirmed in MDMs and lung macrophages. Carbachol stimulated release of LTB(4) from lung macrophages (buffer 222.3 ± 75.1 versus carbachol 1,118 ± 622.4 pg · mL(-1); n = 15, p<0.05) but not IL-6 or IL-8. LTB(4) release was attenuated by the M(3) antagonist, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP; half maximal effective concentration 5.2 ± 2.2 nM; n = 9). Stimulation of macrophage M(3) receptors promotes release of LTB(4), suggesting that anti-muscarinic agents may be anti-inflammatory.
AU  - Koarai,A
AU  - Traves,SL
AU  - Fenwick,PS
AU  - Brown,SM
AU  - Chana,KK
AU  - Russell,RE
AU  - Nicholson,AG
AU  - Barnes,PJ
AU  - Donnelly,LE
DO  - 10.1183/09031936.00136710
EP  - 704
PY  - 2012///
SP  - 698
TI  - Expression of muscarinic receptors by human macrophages.
T2  - Eur Respir J
UR  - http://dx.doi.org/10.1183/09031936.00136710
UR  - http://www.ncbi.nlm.nih.gov/pubmed/21885397
UR  - http://hdl.handle.net/10044/1/18977
VL  - 39
ER  -
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