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Cholinergic pathway suppresses pulmonary innate immunity facilitating pneumonia after stroke

Item Type:Article
Title:Cholinergic pathway suppresses pulmonary innate immunity facilitating pneumonia after stroke
Creators Name:Engel, O. and Akyuez, L. and da Costa Goncalves, A.C. and Winek, K. and Dames, C. and Thielke, M. and Herold, S. and Böttcher, C. and Priller, J. and Volk, H.D. and Dirnagl, U. and Meisel, C. and Meisel, A.
Abstract:Background and Purpose: Temporary immunosuppression has been identified as a major risk factor for the development of pneumonia after acute central nervous system injury. Although overactivation of the sympathetic nervous system was previously shown to mediate suppression of systemic cellular immune responses after stroke, the role of the parasympathetic cholinergic anti-inflammatory pathway in the antibacterial defense in lung remains largely elusive. Methods: The middle cerebral artery occlusion model in mice was used to examine the influence of the parasympathetic nervous system on poststroke immunosuppression. We used heart rate variability measurement by telemetry, vagotomy, {alpha}7 nicotinic acetylcholine receptor–deficient mice, and parasympathomimetics (nicotine, PNU282987) to measure and modulate parasympathetic activity. Results: Here, we demonstrate a rapidly increased parasympathetic activity in mice after experimental stroke. Inhibition of cholinergic signaling by either vagotomy or by using {alpha}7 nicotinic acetylcholine receptor–deficient mice reversed pulmonary immune hyporesponsiveness and prevented pneumonia after stroke. In vivo and ex vivo studies on the role of {alpha}7 nicotinic acetylcholine receptor on different lung cells using bone marrow chimeric mice and isolated primary cells indicated that not only macrophages but also alveolar epithelial cells are a major cellular target of cholinergic anti-inflammatory signaling in the lung. Conclusions: Thus, cholinergic pathways play a pivotal role in the development of pulmonary infections after acute central nervous system injury.
Keywords:Bone Marrow Chimeric Mice, Cholinergic Anti-Inflammatory Pathway, Pneumonia, Parasympathetic Nervous System, Stroke-Induced Immunodepression, Animals, Mice
Publisher:Lippincott Williams & Wilkins
Page Range:3232-3240
Date:November 2015
Official Publication:https://doi.org/10.1161/STROKEAHA.115.008989
PubMed:View item in PubMed

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