Cigarette smoke-exposed neutrophils die unconventionally but are rapidly phagocytosed by macrophages

Cell Death Dis. 2011 Mar 17;2(3):e131. doi: 10.1038/cddis.2011.13.


Pulmonary accumulation of neutrophils is typical for active smokers who are also predisposed to multiple inflammatory and infectious lung diseases. We show that human neutrophil exposure to cigarette smoke extract (CSE) leads to an atypical cell death sharing features of apoptosis, autophagy and necrosis. Accumulation of tar-like substances in autophagosomes is also apparent. Before detection of established cell death markers, CSE-treated neutrophils are effectively recognized and non-phlogistically phagocytosed by monocyte-derived macrophages. Blockade of LOX-1 and scavenger receptor A, but not MARCO or CD36, as well as pre-incubation with oxLDL, inhibited phagocytosis, suggesting that oxLDL-like structures are major phagocytosis signals. Specific lipid (β-carotene and quercetin), but not aqueous, antioxidants increased the pro-phagocytic effects of CSE. In contrast to non-phlogistic phagocytosis, degranulation of secondary granules, as monitored by lactoferrin release, was apparent on CSE exposure, which is likely to promote pulmonary inflammation and tissue degradation. Furthermore, CSE-exposed neutrophils exhibited a compromised ability to ingest the respiratory pathogen, Staphylococcus aureus, which likely contributes to bacterial persistence in the lungs of smokers and is likely to promote further pulmonary recruitment of neutrophils. These data provide mechanistic insight into the lack of accumulation of apoptotic neutrophil populations in the lungs of smokers and their increased susceptibility to degradative pulmonary diseases and bacterial infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Cells, Cultured
  • Humans
  • Macrophages / immunology*
  • Neutrophils / cytology*
  • Neutrophils / immunology
  • Phagocytosis*
  • Pulmonary Disease, Chronic Obstructive / genetics
  • Pulmonary Disease, Chronic Obstructive / immunology
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Scavenger Receptors, Class A / genetics
  • Scavenger Receptors, Class A / immunology
  • Scavenger Receptors, Class E / genetics
  • Scavenger Receptors, Class E / immunology
  • Smoking / adverse effects
  • Smoking / genetics
  • Smoking / immunology*
  • Smoking / physiopathology


  • OLR1 protein, human
  • Scavenger Receptors, Class A
  • Scavenger Receptors, Class E