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

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

doi:10.1186/1465-9921-10-111

Brendan J Carolan, Ben-Gary Harvey + Show 4 more

Open Access

https://doi.org/10.1186/1465-9921-10-111

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Journal: Respiratory research	Publication Date: Nov 17, 2009
Citations: 61	License type: cc-by

Affiliation: Cornell University

Abstract

BackgroundThe 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?MethodsUsing 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.ResultsOf 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.ConclusionThus, 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 RegistrationClinicalTrials.gov ID: NCT00224185 and NCT00224198

Highlights

Oxidants, free radicals with one or more unpaired electrons that are highly reactive, remove electrons from other molecules, changing their structure and function [1]
We asked the question: with the knowledge that both the small airway epithelium and alveolar macrophages are exposed to the same oxidant stress of cigarette smoke and that the small airway epithelium becomes disordered and dysfunctional while alveolar macrophages become activated, are there differences in the program of oxidantrelated gene expression in small airway epithelium and alveolar macrophages in response to smoking?
Study Population Small airway samples and alveolar macrophages were collected from 19 healthy nonsmokers and 30 healthy smokers (Table 1)

Summary

Introduction

Free radicals with one or more unpaired electrons that are highly reactive, remove electrons from other molecules, changing their structure and function [1]. Alveolar macrophages, mesodermderived phagocytic cells capable of releasing oxidants when activated, respond in a hierarchical fashion to incremental levels of oxidative stress, becoming activated, and play a role in mediating damage to other cells but do not become diseased per se [10,19,20] In this context, we asked the question: with the knowledge that both the small airway epithelium and alveolar macrophages are exposed to the same oxidant stress of cigarette smoke and that the small airway epithelium becomes disordered and dysfunctional while alveolar macrophages become activated, are there differences in the program of oxidantrelated gene expression in small airway epithelium and alveolar macrophages in response to smoking?. 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?

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Conclusion