Activation of the alpha7 nAChR reduces acid-induced acute lung injury in mice and rats

Am J Respir Cell Mol Biol. 2007 Aug;37(2):186-92. doi: 10.1165/rcmb.2006-0240OC. Epub 2007 Apr 12.


New evidence indicates that neural mechanisms can down-regulate acute inflammation. In these studies, we tested the potential role of the alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) in a rodent model of acid-induced acute lung injury. We first determined that the alpha7 nAChR was expressed by alveolar macrophages and lung epithelial cells. Then, using an acid-induced acute lung injury mouse model, we found that nicotine, choline, and PNU-282,987 (a specific alpha7 nAChR agonist) decreased excess lung water and lung vascular permeability, and reduced protein concentration in the bronchoalveolar lavage (BAL). Deficiency of alpha7 nAChR resulted in a 2-fold increase in excess lung water and lung vascular permeability. The reduction of proinflammatory cytokines (macrophage inflammatory protein-2 and TNF-alpha) in the BAL with nicotine probably resulted from the suppression of NF-kappaB activation in alveolar macrophages. The beneficial effect of nicotine was also tested in rat model of acid-induced acute lung injury in which BAL protein and receptor for advanced glycation end products (RAGE), a marker of type I cell injury, were reduced by nicotine treatment. These results indicate that activation of alpha7 nAChR may provide a new therapeutic pathway for the treatment of acute lung injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzamides / metabolism
  • Bridged Bicyclo Compounds / metabolism
  • Capillary Permeability / drug effects
  • Cell Differentiation
  • Cells, Cultured
  • Choline / metabolism
  • Cytokines / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Extravascular Lung Water / metabolism
  • Humans
  • Hydrochloric Acid* / pharmacology
  • Hydrochloric Acid* / toxicity
  • Lung / cytology
  • Lung / drug effects*
  • Lung / pathology*
  • Macrophages, Alveolar / cytology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / metabolism
  • Neutrophils / cytology
  • Neutrophils / physiology
  • Nicotine / metabolism
  • Nicotine / pharmacology
  • Nicotinic Agonists / metabolism
  • Nicotinic Agonists / pharmacology
  • Rats
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / metabolism*
  • Respiratory Distress Syndrome* / chemically induced
  • Respiratory Distress Syndrome* / pathology
  • alpha7 Nicotinic Acetylcholine Receptor


  • Benzamides
  • Bridged Bicyclo Compounds
  • Chrna7 protein, human
  • Chrna7 protein, mouse
  • Chrna7 protein, rat
  • Cytokines
  • NF-kappa B
  • Nicotinic Agonists
  • PNU-282987
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • Nicotine
  • Choline
  • Hydrochloric Acid