Innate Immune Functions of the Airway Epithelium
128
Citation
58
Reference
10
Related Paper
Citation Trend
Abstract:
The epithelium of the respiratory tract forms a large surface area that maintains intimate contact with the environment. Through the act of breathing, this mucosal surface encounters an array of pathogens and toxic particulates. In response to these challenges many strategies have evolved to protect the host. These include the barrier functions of the epithelium, cough, mucociliary clearance, resident professional phagocytes, and the secretion of a number of proteins and peptides with host defense functions. Thus, the surface and submucosal gland epithelium of the conducting airways is a constitutive primary participant in innate immunity. In addition, this tissue may serve the function of a secondary amplifier of innate immune responses following neurohumoral input, stimulation with cytokines from cells such as alveolar macrophages, or engagement of pattern recognition receptors. Here, we provide an overview of the airway epithelium's role in pulmonary innate immunity, especially in the context of bacterial and viral infections, emphasizing findings from human cells and selected animal models. We also provide examples of human disease states caused by impaired epithelial defenses in the lung.Keywords:
Respiratory tract
Innate lymphoid cell
Mucociliary clearance
Alveolar Epithelium
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
Alveolar Epithelium
Alveolar macrophage
Cite
Citations (22)
The objective of the study was to develop a scintigraphic method for measurement of airway mucociliary clearance in small laboratory rodents such as the mouse. Previous investigations have characterized the secretory cell types present in the mouse airway, but analysis of the mucus transport system has been limited to in vitro examination of tissue explants or invasive in vivo measures of a single airway, the trachea. Three methods were used to deposit insoluble, radioisotopic colloidal particles: oropharyngeal aspiration, intratracheal instillation, and nose-only aerosol inhalation. The initial distribution of particles within the lower respiratory tract was visualized by γ-camera, and clearance of particles was followed intermittently over 6 h and at the conclusion, 24 h postdelivery. Subsets of mice underwent lavage for evidence of tissue inflammation, and others were restudied for reproducibility of the methods. The aspiration and instillation methods of delivery led to greater distributions of deposited activity within the lungs, i.e., ∼60–80% of the total respiratory tract radioactivity, whereas the nose-only aerosol technique attained a distribution of 32% to the lungs. However, the aerosol technique maximized the fraction of particles that cleared the airway over a 24-h period, i.e, deposited onto airway epithelial surfaces and cleared by mucociliary function such that lung retention at 24 h averaged 57% for delivery by aerosol inhalation and ≥80% for the aspiration or intratracheal instillation techniques. Particle delivery methods did not cause lung inflammation/injury with use of inflammatory cells and chemoattractant cytokines as criteria. Scintigraphy can discern particle deposition and clearance from the lower respiratory tract in the mouse, is noninvasive and reproducible, and includes the capability for restudy and lung lavage when time course or chronic treatments are being considered.
Mucociliary clearance
Respiratory tract
Clearance
Particle deposition
Cite
Citations (141)
SUMMARY Tracheal mucociliary clearance was determined in horses by measuring the rostrad transport of the radiopharmaceutical 99m technetium‐sulphur colloid following deposition on the tracheal epithelium by intratracheal injection. The effects of head position (head elevated to normal standing position vs head lowered) and of accumulated purulent secretions on tracheal mucociliary clearance were evaluated for the first time in the horse. In normal horses tracheal mucociliary clearance was greatly accelerated by lowering the head so that the cranial trachea was lower than the caudal trachea. Horses confined with their heads elevated for 24 hours developed an accumulation of purulent airway secretions (and associated increased numbers of bacteria) in the lower respiratory tract and showed a decrease in tracheal mucociliary clearance when compared with their previously measured rate when the lower airway contained only normal secretions. These findings have implications for management practices where horses are prevented from lowering their heads, such as transportation and cross‐tying, which may therefore contribute to lower respiratory tract disease in horses.
Mucociliary clearance
Cite
Citations (63)
Alveolar Epithelium
Pulmonary alveolus
Cite
Citations (5)
It has been already proved in many experimental studies that tobacco smoke has multiple toxic effects on respiratory tract cells. Alterations in cilliary epithelium of rats trachea after short exposition to high tobacco smoke concentrations in inhaled air were been determined in current study. Morphological evaluation revealed in lining epithelium decrease in number of cilliary cells and increase in number of goblet cells. The mucous membrane was thickened and infiltrated with inflammatory cells.
Respiratory tract
Mucous membrane
Cite
Citations (2)
Sinonasal respiratory epithelium is a highly regulated barrier that employs mucociliary clearance (MCC) as the airways first line of defense. The biological properties of the airway surface liquid (ASL), combined with coordinated ciliary beating, are critical components of the mucociliary apparatus. The ASL volume and viscosity is modulated, in part, by the cystic fibrosis transmembrane conductance regulator (CFTR). The CFTR is an anion transporter of chloride (Cl-) and bicarbonate (HCO3-) that is located on the apical surface of respiratory epithelium and exocrine glandular epithelium. Improved understanding of how dysfunction or deficiency of CFTR influences the disease process in both genetically defined cystic fibrosis (CF) and acquired conditions has provided further insight into potential avenues of treatment. This review discusses the latest data regarding acquired CFTR deficiency and use of CFTR specific treatment strategies for CRS and other chronic airway diseases.
Mucociliary clearance
Cite
Citations (28)
Respiratory tract
Alveolar Epithelium
Cite
Citations (12)
Respiratory tract
Barrier function
Cite
Citations (4)
Epithelium lining the tracheobronchial tree represents the first cells with which particulates, gases, microbes, etc., come into contact upon inhalation. Thus, interactions between such inhaled substances and epithelial cells probably are integral to the pathogenesis of several occupational or environmental - related pulmonary lesions, yet such interactions have not yet been elucidated fully. Many published studies have described patterns of deposition within extra- and intrapulmonary airways and alveolar ducts, and histologic and ultrastructural changes in epithelium in vivo in response to inhalation and deposition. However, our knowledge of specific structural and functional responses of airway epithelium on a cellular level is limited, since exposures of animals in vivo or even tissues in situ do not allow for studying intracellular responses, especially subtle sublytic alterations which could be the basis for subsequent pathogenic responses. For this reason, investigators have utilized cell culture systems to examine intracellular mechanisms related to responses of respiratory epithelium to deleterious substances which may be inhaled in an occupational or environmental setting.
Respiratory tract
Alveolar Epithelium
Cite
Citations (0)
The lung surface of air‐breathing vertebrates is formed by a continuous epithelium that is covered by a fluid layer. In the airways, this epithelium is largely pseudostratified consisting of diverse cell types such as ciliated cells, goblet cells, and undifferentiated basal cells, whereas the alveolar epithelium consists of alveolar type I and alveolar type II cells. Regulation and maintenance of the volume and viscosity of the fluid layer covering the epithelium is one of the most important functions of the epithelial barrier that forms the outer surface area of the lungs. Therefore, the epithelial cells are equipped with a wide variety of ion transport proteins, among which Na + , Cl − , and K + channels have been identified to play a role in the regulation of the fluid layer. Malfunctions of pulmonary epithelial ion transport processes and, thus, impairment of the liquid balance in our lungs is associated with severe diseases, such as cystic fibrosis and pulmonary oedema. Due to the important role of pulmonary epithelial ion transport processes for proper lung function, the present paper summarizes the recent findings about composition, function, and ion transport properties of the airway epithelium as well as of the alveolar epithelium.
Alveolar Epithelium
Cite
Citations (146)