title: In utero nicotine exposure promotes M2 activation in neonatal mouse alveolar macrophages.
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 the function of the neonatal alveolar macrophage (AM), 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 interleukin-13 and transforming growth factor-β1 (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.
  
  
  CONCLUSIONS
  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 toward alternative activation. These findings have important implications for immune responses in the nicotine-exposed neonatal lung.
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. cwongtr@emory.edu
authors.forename: Cherry
authors.initials: C
authors.lastname: Wongtrakool
authors.forename: Kora
authors.initials: K
authors.lastname: Grooms
authors.forename: Xiao-Du
authors.initials: XD
authors.lastname: Ping
authors.forename: Hilda
authors.initials: H
authors.lastname: Rivera
authors.forename: Janine
authors.initials: J
authors.lastname: Ward
authors.forename: Susanne
authors.initials: S
authors.lastname: Roser-Page
authors.forename: Jesse
authors.initials: J
authors.lastname: Roman
authors.forename: Lou Ann S
authors.initials: LA
authors.lastname: Brown
authors.forename: Theresa W
authors.initials: TW
authors.lastname: Gauthier
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002038:Bungarotoxins; D002460:Cell Line; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D019899:Paracrine Communication / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology*; D060888:Real-Time Polymerase Chain Reaction; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: D002038:Bungarotoxins; C579166:Chrna7 protein, mouse; D005353:Fibronectins; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine