Acute cigarette smoke exposure induces apoptosis of alveolar macrophages

Am J Physiol Lung Cell Mol Physiol. 2001 Dec;281(6):L1392-401. doi: 10.1152/ajplung.2001.281.6.L1392.


Alveolar macrophages (AMs) may play a critical role in cigarette smoke (CS)-related pulmonary diseases. This study was designed to determine whether CS induces apoptosis of AMs. In in vitro studies, mouse, rat, and human AMs and human blood monocyte-derived macrophages cultured with aqueous whole CS extracts underwent apoptosis that was detected by light and electron microscopy and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling. The gas phase of CSE did not cause apoptosis. The CS-induced apoptosis was associated with increased oxidative stress, Bax protein accumulation, mitochondrial dysfunction, and mitochondrial cytochrome c release but was independent of p53, Fas, and caspase activation. This apoptosis was inhibited by antioxidants such as glutathione, ascorbic acid, and alpha-tocopherol. In in vivo studies where rats were exposed to the smoke from 10 cigarettes over 5 h in an exposure chamber, approximately 3% of AMs obtained by bronchoalveolar lavage after 24 h showed apoptosis. These results suggest that acute CS exposure is capable of inducing apoptosis of AMs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Apoptosis*
  • Caspases / metabolism
  • Electron Transport Complex IV / metabolism
  • Humans
  • In Situ Nick-End Labeling
  • In Vitro Techniques
  • Lung Diseases / metabolism
  • Lung Diseases / pathology
  • Macrophages, Alveolar / metabolism
  • Macrophages, Alveolar / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria / metabolism
  • Oxidative Stress
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2*
  • Rats
  • Rats, Sprague-Dawley
  • Smoking / adverse effects*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein
  • fas Receptor / metabolism


  • BAX protein, human
  • Bax protein, mouse
  • Bax protein, rat
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • fas Receptor
  • Electron Transport Complex IV
  • Caspases