In Utero Nicotine Exposure Promotes M2 Activation in Neonatal Mice Alveolar Macrophages

• Type of Material: Article
• Authors: Cherry Wongtrakool, Emory University; Kora Grooms, Emory University; Xiao-Du Ping, Emory University; Hilda Rivera, Emory University; Janine Ward, Emory University; Susanne Roser-Page, Atlanta Veterans Affairs Medical Center; Jesse Roman, University of Louisville; Lou Ann Brown, Emory University; Theresa Gauthier, Emory University
• Language: English
• Date: 2012-08
• Publisher: Nature Publishing Group: Open Access Hybrid Model Option A
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 International Pediatric Research Foundation, Inc.
• Final Published Version (URL): http://www.nature.com/pr/journal/v72/n2/full/pr201255a.html
• Title of Journal or Parent Work: Pediatric Research
• ISSN: 0031-3998
• Volume: 72
• Issue: 2
• Start Page: 147
• End Page: 153
• Grant/Funding Information: Funded by National Institutes of Health Grant K08 HL080293 (to C.W.) and Children’s Center for Developmental Lung Biology (to T.W.G., L.A.B.).
• Research Categories: Health Sciences, Obstetrics and Gynecology; Health Sciences, Medicine and Surgery

Abstract

Background Maternal smoking in utero has been associated with adverse health outcomes including lower respiratory tract infections in infants and children, but the mechanisms underlying these associations continue to be investigated. We hypothesized that nicotine plays a significant role in mediating the effects of maternal tobacco smoke on neonatal alveolar macrophage (AM) function, the resident immune cell in the neonatal lung. Methods Primary AMs were isolated at postnatal day 7 from a murine model of in utero nicotine exposure. The murine AM cell line MH-S was used for additional in vitro studies. Results In utero nicotine increased IL-13 and transforming growth factor beta one (TGFβ1) in the neonatal lung. Nicotine-exposed AMs demonstrated increased TGFβ1 and increased markers of alternative activation with diminished phagocytic function. However, AMs from mice deficient in the α7 nicotinic acetylcholine receptor (α7 nAChR) had less TGFβ1, reduced alternative activation and improved phagocytic functioning despite similar in utero nicotine exposure. Conclusion In utero nicotine exposure, mediated in part via the α7 nAChR, may increase the risk of lower respiratory tract infections in neonates by changing the resting state of AM towards alternative activation. These findings have important implications for immune responses in the nicotine-exposed neonatal lung.