Cholinergic Pathway Suppresses Pulmonary Innate Immunity Facilitating Pneumonia After Stroke
| Autor: | Katarzyna Winek, Josef Priller, Andrey C. da Costa Goncalves, Claudia Dames, Christian Meisel, Mareike Thielke, Odilo Engel, Ulrich Dirnagl, Chotima Böttcher, Levent Akyüz, Hans-Dieter Volk, Susanne Herold, Andreas Meisel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Sympathetic nervous system
medicine.medical_treatment microbiology [Pneumonia] Vagotomy Receptors Nicotinic pharmacology [Benzamides] immunology [Macrophages Alveolar] drug effects [Respiratory Mucosa] Parasympathetic nervous system Mice Heart Rate Nicotinic Agonists Chrna9 protein mouse Lung pharmacology [Nicotinic Agonists] Mice Knockout immunology [Respiratory Mucosa] immunology [Parasympathetic Nervous System] drug effects [Parasympathetic Nervous System] Infarction Middle Cerebral Artery Stroke medicine.anatomical_structure Nicotinic agonist drug effects [Macrophages Alveolar] immunology [Pneumonia] Parasympathomimetics Benzamides drug effects [Heart Rate] immunology [Heart Rate] Cardiology and Cardiovascular Medicine Bronchoalveolar Lavage Fluid Acetylcholine medicine.drug Signal Transduction genetics [Receptors Nicotinic] Nicotine immunology [Infarction Middle Cerebral Artery] drug effects [Immunity Innate] Respiratory Mucosa PNU-282987 Bridged Bicyclo Compounds Parasympathetic Nervous System Macrophages Alveolar medicine drug effects [Lung] Animals microbiology [Bronchoalveolar Lavage Fluid] ddc:610 Cholinergic anti-inflammatory pathway pharmacology [Bridged Bicyclo Compounds] Advanced and Specialized Nursing immunology [Lung] business.industry pharmacology [Nicotine] microbiology [Lung] Pneumonia Immunity Innate immunology [Immunity Innate] Mice Inbred C57BL Disease Models Animal immunology [Receptors Nicotinic] Immunology pharmacology [Parasympathomimetics] Cholinergic Neurology (clinical) business immunology [Stroke] |
| Zdroj: | Stroke 46(11), 3232-3240 (2015). doi:10.1161/STROKEAHA.115.008989 |
| DOI: | 10.1161/STROKEAHA.115.008989 |
| Popis: | 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, α7 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 α7 nicotinic acetylcholine receptor–deficient mice reversed pulmonary immune hyporesponsiveness and prevented pneumonia after stroke. In vivo and ex vivo studies on the role of α7 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. |
| Databáze: | OpenAIRE |
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