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• W2168044147 abstract "Infectious complications, predominantly pneumonia, are the most common cause of death in the postacute phase of stroke, although the mechanisms underlying the corresponding immunosuppression are not fully understood. We tested the hypothesis that activation of the α7 nicotinic acetylcholine receptor (α7nAChR) pathway is important in the stroke-induced increase in lung injury caused by Pseudomonas aeruginosa pneumonia in mice. Prior stroke increased lung vascular permeability caused by P. aeruginosa pneumonia and was associated with decreased lung neutrophil recruitment and bacterial clearance in mice. Pharmacologic inhibition (methyllycaconitine IC50: 0.2–0.6 nM) or genetic deletion of the α7nAChR significantly (P< 0.05) attenuates the effect of prior stroke on lung injury and mortality caused by P. aeruginosa pneumonia in mice. Finally, pretreatment with PNU-282987, a pharmacologic activator of the α7nAChR (EC50: 0.2 μM), significantly (P<0.05) increased lung injury caused by P. aeruginosa pneumonia, significantly (P<0.05) decreased the release of KC, a major neutrophil chemokine, and significantly (P<0.05) decreased intracellular bacterial killing by a mouse alveolar macrophage cell line and primary mouse neutrophils. In summary, the α7 nicotinic cholinergic pathway plays an important role in mediating the systemic immunosuppression observed after stroke and directly contributes to more severe lung damage induced by P. aeruginosa.—Lafargue, M., Xu, L., Carles, M., Serve, E., Anjum, N., Iles, K. E., Xiong, X., Giffard, R., Pittet, J.-F. Stroke-induced activation of the α7 nicotinic receptor increases Pseudomonas aeruginosa lung injury. FASEB J. 26, 2919–2929 (2012). www.fasebj.org" @default.
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• W2168044147 date "2012-04-09" @default.
• W2168044147 modified "2023-10-02" @default.
• W2168044147 title "Stroke‐induced activation of the α7 nicotinic receptor increases<i>Pseudomonas aeruginosa</i>lung injury" @default.
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• W2168044147 doi "https://doi.org/10.1096/fj.11-197384" @default.
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