title: Critical role of aldehydes in cigarette smoke-induced acute airway inflammation.
abstract: BACKGROUND
  Cigarette smoking (CS) is the most important risk factor for COPD, which is associated with neutrophilic airway inflammation. We hypothesize, that highly reactive aldehydes are critical for CS-induced neutrophilic airway inflammation.
  
  
  METHODS
  BALB/c mice were exposed to CS, water filtered CS (WF-CS) or air for 5 days. Levels of total particulate matter (TPM) and aldehydes in CS and WF-CS were measured. Six hours after the last exposure, inflammatory cells and cytokine levels were measured in lung tissue and bronchoalveolar lavage fluid (BALF). Furthermore, Beas-2b bronchial epithelial cells were exposed to CS extract (CSE) or WF-CS extract (WF-CSE) in the absence or presence of the aldehyde acrolein and IL-8 production was measured after 24 hrs.
  
  
  RESULTS
  Compared to CS, in WF-CS strongly decreased (CS; 271.1 ± 41.5 μM, WF-CS; 58.5 ± 8.2 μM) levels of aldehydes were present whereas levels of TPM were only slightly reduced (CS; 20.78 ± 0.59 mg, WF-CS; 16.38 ± 0.36 mg). The numbers of mononuclear cells in BALF (p<0.01) and lung tissue (p<0.01) were significantly increased in the CS- and WF-CS-exposed mice compared to air control mice. Interestingly, the numbers of neutrophils (p<0.001) in BALF and neutrophils and eosinophils (p<0.05) in lung tissue were significantly increased in the CS-exposed but not in WF-CS-exposed mice as compared to air control mice. Levels of the neutrophil and eosinophil chemoattractants KC, MCP-1, MIP-1α and IL-5 were all significantly increased in lung tissue from CS-exposed mice compared to both WF-CS-exposed and air control mice. Interestingly, depletion of aldehydes in WF-CS extract significantly reduced IL-8 production in Beas-2b as compared to CSE, which could be restored by the aldehyde acrolein.
  
  
  CONCLUSIONS
  Aldehydes present in CS play a critical role in inflammatory cytokine production and neutrophilic- but not mononuclear airway inflammation.
authors.affiliation: Department of Pathology & Medical Biology, Laboratory Allergology & Pulmonary Diseases, Hanzeplein 1, Groningen, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: van der Toorn
authors.forename: Dirk-Jan
authors.initials: DJ
authors.lastname: Slebos
authors.forename: Harold G
authors.initials: HG
authors.lastname: de Bruin
authors.forename: Renee
authors.initials: R
authors.lastname: Gras
authors.forename: Delaram
authors.initials: D
authors.lastname: Rezayat
authors.forename: Lucie
authors.initials: L
authors.lastname: Jorge
authors.forename: Koen
authors.initials: K
authors.lastname: Sandra
authors.forename: Antoon J M
authors.initials: AJ
authors.lastname: van Oosterhout
mesh_terms: D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D016207:Cytokines / Q000276:immunology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D018375:Neutrophil Activation / Q000187:drug effects / Q000276:immunology*; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology*; D012907:Smoking / Q000009:adverse effects*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D000447:Aldehydes; D016207:Cytokines; D014028:Tobacco Smoke Pollution