Alpha7 nicotinic acetylcholine receptor in macrophage apoptosis and efferocytosis

Abstract

The development of atherosclerotic lesions depends on an important inflammatory component mediated mostly by macrophages. Notably, apoptosis of macrophages within the lesion and efficient clearance of apoptotic cells are key factors in lesion progression. In this context we are interested in defining whether non‐neuronal nicotinic acetylcholine receptors (nAChR) play a role in modulation of macrophage survival and clearance of apoptotic cells. Specifically, the α7nAChR (α7) was found to mediate, in vitro, survival pathways in endothelial cells and lymphocytes. However, it remains to be determined whether macrophage α7 can modulate cell survival and efferocytosis. The objective of our study is to explore the contribution of pathways downstream of α7 stimulation to macrophage survival as well as effective efferocytosis using a combination of pharmacological and biochemical approaches. In bone marrow‐derived macrophages we observed activation of ERK1/2 upon treatment with nicotine which was abrogated by α‐bungarotoxin, suggesting that the actions of nicotine are mediated by α7. These findings will help outline the potential roles of α7nAChR in regulation of macrophage apoptosis and efferocytosis. Supported by R01HL111877‐01