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Valentin A Pavlov, Kui Cui, Meghan Addorisio, David L Williams, Valentin Yakubenko, The α7 nicotinic acetylcholine receptor is an important determinant of monocyte-derived macrophage migration, The Journal of Immunology, Volume 204, Issue 1_Supplement, May 2020, Page 220.25, https://doi.org/10.4049/jimmunol.204.Supp.220.25
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Abstract
Inflammation is regulated by the nervous system. The α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages plays a key role in this regulation by meditating cholinergic suppression of pro-inflammatory cytokine release within the vagus nerve-based inflammatory reflex during endotoxemia and other conditions. However, the involvement of of α7nAChR in other macrophage functions remains poorly understood. The objective of this study was to provide insight into the role of α7nAChR in macrophage migration and accumulation in organs during murine endotoxemia. Briefly, monocyte progenitors isolated from bone marrow of wild type (WT) and α7nAChR knockout (KO) mice were labeled with red PKH26 (WT) or green PKH67 (α7nAChR−/−) fluorescent dyes, mixed in equal amounts and injected in tail vein of WT mice 20 min before LPS administration. 48 hours later, lungs, livers and spleens were isolated, digested and analyzed using multicolor flow cytometry (Fortessa-X20) and imaging flow cytometry (ImageStream X Mark II). α7nAChR deficiency resulted in significantly decreased accumulation of macrophages in liver (~10 folds), lung (~4 folds) and spleen (~3 folds) (P<0.01). The morphology of migrated macrophage was verified by imaging flow cytometry. These results identify α7nAChR as an important determinant of the recruitment of monocytes to the site of acute inflammation. They also provide a rationale for further studies on the molecular mechanisms, including the involvement of adhesive receptors in α7nAChR-dependent monocyte/macrophage migration.