RT Journal Article SR Electronic T1 Muscarinic M3 receptors on structural cells regulate neutrophilic inflammation in mice JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP P869 VO 44 IS Suppl 58 A1 Loes Kistemaker A1 Ronald Van Os A1 Bertien Ausema A1 Sophie Bos A1 Machteld Hylkema A1 Pieter Hiemstra A1 Jurgen Wess A1 Herman Meurs A1 Huib Kerstjens A1 Reinoud Gosens YR 2014 UL http://erj.ersjournals.com/content/44/Suppl_58/P869.abstract AB IntroductionAnticholinergics, which block the M3 receptor, are effective bronchodilators for patients with COPD. Recent evidence from M3 receptor deficient mice (M3R-/-) indicates that M3 receptors also regulate neutrophilic inflammation in response to cigarette smoke (CS). M3 receptors are present on almost all cell types and in this study we investigated the relative contribution of the M3 receptor on structural cells versus hematopoietic cells to CS-induced inflammation using chimeric mice.MethodsChimeric animals were generated and after 10 weeks engraftment was analyzed by flow-cytometry. Thereafter, irradiated and non-irradiated control animals were exposed to CS or fresh air for four consecutive days.ResultsEngraftment was high and not different between the groups. CS exposure induced a small, nonsignificant increase in macrophage numbers in BALF in all groups (1.3-1.4 fold). No increase in lymphocyte numbers was observed. CS induced a significant increase in neutrophil numbers in non-irradiated and irradiated control animals (4-35 fold). Interestingly, WT animals receiving M3-/- bone marrow showed a similar increase in neutrophil number (15-fold). In contrast, no increase in the number of neutrophils was observed in M3R-/- animals receiving WT bone marrow. The increase in KC levels was similar in all smoke-exposed groups, both on mRNA (2.8-5.0 fold) and protein level (2.5-9.6 fold). No increase in IL-6 expression was observed.ConclusionsThese findings suggest that the M3 receptor on structural cells plays a pro-inflammatory role in CS-induced neutrophilic inflammation, whereas the M3 receptor on hematopoietic cells does not. This effect is probably not mediated via IL-6 or IL-8 release.