Differential Gene Expression in Human Conducting Airway Surface Epithelia and Submucosal Glands

Abstract

Human conducting airways contain two anatomically distinct epithelial cell compartments: surface epithelium and submucosal glands (SMG). Surface epithelial cells interface directly with the environment and function in pathogen detection, fluid and electrolyte transport, and mucus elevation. SMG secrete antimicrobial molecules and most of the airway surface fluid. Despite the unique functional roles of surface epithelia and SMG, little is known about the differences in gene expression and cellular metabolism that orchestrate the specialized functions of these epithelial compartments. To approach this problem, we performed large-scale transcript profiling using epithelial cell samples obtained by laser capture microdissection (LCM) of human bronchus specimens. We found that SMG expressed high levels of many transcripts encoding known or putative innate immune factors, including lactoferrin, zinc a-2 glycoprotein, and proline-rich protein 4. By contrast, surface epithelial cells expressed high levels of genes involved in basic nutrient catabolism, xenobiotic clearance, and ciliated structure assembly. Selected confirmation of differentially expressed genes in surface and SMG epithelia demonstrated the predictive power of this approach in identifying genes with localized tissue expression. To characterize metabolic differences between surface epithelial cells and SMG, immunostaining for a mitochondrial marker (isocitrate dehydrogenase) was performed. Because greater staining was observed in the surface compartment, we predict that these cells use significantly more energy than SMG cells. This study illustrates the power of LCM in defining the roles of specific anatomic features in airway biology and may be useful in examining how disease states alter transcriptional programs in the conducting airways.Keywords: airway epithelia; microarray; submucosal glandThe airways maintain a dynamic interface with the environment. The continuity of the airway epithelium serves as a physical barrier to inhaled pathogens, while the secreted protein and peptide products of the tissue, in concert with ciliary function, support mucociliary clearance and host defense. The epithelium of the intrapulmonary airways contributes to pulmonary innate immunity as a first responder and as an important site of signal amplification. Through a variety of receptor systems, the surface epithelial cells sense and respond to inhaled chemical, microbial, thermal, and particulate stimuli to maintain health. Perturbation of the function of this tissue is involved in the pathogenesis of several diseases, including asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF).The epithelial tissue of the conducting airways includes many specialized cell types and the spatial division of functions. Two anatomically distinct conducting airway compartments are the airway surface epithelium and submucosal glands (SMG). The surface epithelium of the cartilaginous conducting airways is composed of ciliated, nonciliated, goblet, and basal cell ty...

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