Critical role of aldehydes in cigarette smoke-induced acute airway inflammation

Respiratory Research

Antoon JM van Oosterhout³  Koen Sandra¹  Lucie Jorge¹  Delaram Rezayat³  Renee Gras³  Harold G de Bruin³  Dirk-Jan Slebos²  Marco van der Toorn⁴ 

[1] Metablys, Research Institute for Chromatography, President Kennedypark 26, Kortrijk, 8500, Belgium;Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, PO Box 30001, Groningen, RB, 9700, The Netherlands;GRIAC Research Institute, Groningen, The Netherlands;Department of Laboratory Medicine, Groningen, The Netherlands

关键词: COPD;    Airway inflammation;    Mouse model;    Aldehydes;    Cigarette smoke;   

Others  :  794740
DOI  :  10.1186/1465-9921-14-45

 received in 2012-12-10, accepted in 2013-03-07,  发布年份 2013

【 摘 要 】

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.

Conclusion

Aldehydes present in CS play a critical role in inflammatory cytokine production and neutrophilic- but not mononuclear airway inflammation.

【 授权许可】

   
2013 Toorn et al.; licensee BioMed Central Ltd.

【 图 表 】

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