Abstract
BackgroundCigarette 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.MethodsBALB/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.ResultsCompared 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.ConclusionAldehydes present in CS play a critical role in inflammatory cytokine production and neutrophilic- but not mononuclear airway inflammation.
Highlights
Cigarette smoking (CS) is the most important risk factor for Chronic Obstructive Pulmonary Disease (COPD), which is associated with neutrophilic airway inflammation
water filtered CS (WF-CS) extract (WF-CSE) was produced as described for CSE, but the smoke was first passed through a receptacle of water (1L) before it was bubbled through RPMI 1640, and this was regarded as 100% strength
In this study we demonstrated that depletion of aldehydes in WF-CSE significantly reduced IL-8 production in Beas-2b which could be restored by the aldehyde acrolein
Summary
Cigarette smoking (CS) is the most important risk factor for COPD, which is associated with neutrophilic airway inflammation. Reactive components with unpaired valence shell electrons are not capable of diffusing through the plasma membranes and are rapidly neutralized by enzymatic antioxidants like superoxide dismutase, catalase, glutathione peroxidase and thioredoxin reductase or by nonenzymatic antioxidants glutathione and vitamine c all present in high concentrations in the epithelial lining fluid [9,10,11] In addition to these short-lived reactive components, the gas phase of CS contains more stable oxidizing intermediates that have the potential to induce endogenous oxidative stress and inflammation, including aldehydes such as acetaldehyde, acrolein and crotonaldehyde [12]. Studies in human neutrophils showed that aldehydes are able to inhibit human neutrophil apoptosis, promoting longevity and contribute to neutrophilic accumulation [19] All together these data suggest a critical role for aldehydes in modification of proteins leading to altered protein function and impaired regulation of redox-sensitive factors like NF-κB which may drive the CS-induced neutrophilic airway inflammation [20,21,22]
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