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Comparative Study
. 2009 Nov 17;10(1):111.
doi: 10.1186/1465-9921-10-111.

Disparate oxidant gene expression of airway epithelium compared to alveolar macrophages in smokers

Brendan J Carolan  1 , Ben-Gary Harvey, Neil R Hackett, Timothy P O'Connor, Patricia A Cassano, Ronald G Crystal
Affiliations
Comparative Study

Disparate oxidant gene expression of airway epithelium compared to alveolar macrophages in smokers

Brendan J Carolan et al. Respir Res. .

Abstract

Background: The small airway epithelium and alveolar macrophages are exposed to oxidants in cigarette smoke leading to epithelial dysfunction and macrophage activation. In this context, we asked: what is the transcriptome of oxidant-related genes in small airway epithelium and alveolar macrophages, and does their response differ substantially to inhaled cigarette smoke?

Methods: Using microarray analysis, with TaqMan RT-PCR confirmation, we assessed oxidant-related gene expression in small airway epithelium and alveolar macrophages from the same healthy nonsmoker and smoker individuals.

Results: Of 155 genes surveyed, 87 (56%) were expressed in both cell populations in nonsmokers, with higher expression in alveolar macrophages (43%) compared to airway epithelium (24%). In smokers, there were 15 genes (10%) up-regulated and 7 genes (5%) down-regulated in airway epithelium, but only 3 (2%) up-regulated and 2 (1%) down-regulated in alveolar macrophages. Pathway analysis of airway epithelium showed oxidant pathways dominated, but in alveolar macrophages immune pathways dominated.

Conclusion: Thus, the response of different cell-types with an identical genome exposed to the same stress of smoking is different; responses of alveolar macrophages are more subdued than those of airway epithelium. These findings are consistent with the observation that, while the small airway epithelium is vulnerable, alveolar macrophages are not "diseased" in response to smoking.

Trial registration: ClinicalTrials.gov ID: NCT00224185 and NCT00224198.

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Figures

Figure 1
Figure 1
Expression of oxidant-related genes in small airway epithelium and alveolar macrophages of healthy nonsmokers and healthy smokers. A. Expression of oxidant-related genes in healthy nonsmokers. The % of all oxidant-related genes (total of 155 genes surveyed) that were expressed (defined as Affymetrix detection call of "present" in >50% of nonsmoker individuals, n = 19) is presented on the ordinate and the categories in which these genes are expressed are presented on the abscissa. Each bar represents the % of genes expressed and inside each bar is the corresponding number of oxidant-related genes expressed. B. Expression of oxidant-related genes in healthy smokers. The % of all oxidant-related genes that were expressed in healthy smokers (n = 30) is presented on the ordinate and the categories in which these genes are expressed is presented on the abscissa. Each bar represents the % of genes expressed and inside each bar is the corresponding number of oxidant-related genes expressed.
Figure 2
Figure 2
Relative expression of oxidant-related genes in small airway epithelium compared to alveolar macrophages from the same healthy nonsmokers and healthy smokers. Presented only are those oxidant-related genes expressed (Affymetrix detection call of present in >50% of small airway epithelium or alveolar macrophages) in healthy nonsmokers or healthy smokers. Average relative expression of oxidant-related genes in small airway epithelium is presented on the ordinate and average relative expression of oxidant-related genes in alveolar macrophages is presented on the abscissa. Each point represents one gene. white circle = average expression in healthy nonsmokers; black circle = average relative expression in healthy smokers. The different categories of oxidant-related genes surveyed are presented in panels A-H. A. Glutathione metabolism; B. Redox balance; C. Catalase/superoxide dismutases; D. Other oxidant scavengers; E. Pentose pathway cycle; F. Xenobiotic metabolism; G. Selenium-related; and H. Bilirubin/ascorbic acid related.
Figure 3
Figure 3
Smoking responsiveness of oxidant-related genes expressed in the small airway epithelium and alveolar macrophages of healthy nonsmokers (n = 19) and healthy smokers (n = 30). A. Smoking responsiveness of expressed oxidant-related genes in small airway epithelium. B. Smoking responsiveness of expressed oxidant-related genes in alveolar macrophages. For both A and B, the ordinate shows p value and the abscissa shows fold-change. Each data point represents 1 oxidant-related gene. Grey = oxidant-related genes that are not significantly changed (p > 0.05 and/or fold-change up or down <1.5) in small airway epithelium or alveolar macrophages of normal smokers compared to normal nonsmokers. Blue = oxidant-related genes that are smoking responsive or significantly changed (p < 0.05, fold change up or down ≥1.5) in the small airway epithelium; red = oxidant-related genes that are smoking responsive or significantly changed in alveolar macrophages of healthy smokers compared to healthy nonsmokers.
Figure 4
Figure 4
Percentage of the total of 155 oxidant-related genes surveyed that are smoking responsive in small airway epithelium and alveolar macrophages. A. Oxidant-related genes whose expression is up-regulated in healthy smokers compared to healthy nonsmokers. B. Oxidant-related genes whose expression is down-regulated in healthy smokers compared to healthy nonsmokers. For both A and B, the percentage of oxidant-related genes up or down-regulated are presented on the ordinate and the different categories are presented on the abscissa; within each bar is the number of genes modified.
Figure 5
Figure 5
Comparison of the fold-changes of smoking responsive oxidant-related genes in the small airway epithelium and alveolar macrophages in the different oxidant-related gene categories. A. Fold-change of smoking responsive oxidant-related genes in small airway epithelium. B. Fold-change of smoking responsive oxidant-related genes in alveolar macrophages. For both A and B, the fold-change is presented on the ordinate and the oxidant-related genes in their categories on the abscissa. Each bar represents the fold-change (average expression in healthy smokers compared to average expression in healthy nonsmokers) of an oxidant related gene in the corresponding category and error bars represent the standard error for the ratio.
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