Long-Lasting Effects of Chronic Ozone Exposure on Rat Nasal Epithelium
Jack R. HarkemaJon A. HotchkissEdward B. BarrCatherine B. BennettMarianne GallupJong Kwon LeeCarol Basbaum
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Section:ChooseTop of pageAbstract <The airway epithelium plays an important role in host defense as a barrier against physical, pathological and chemical stimuli. The epithelium is also an active metabolic and biosynthetic site for production and release of mediators, such as arachidonic acid metabolites, cytokines and a putative epithelium-derived refaxing factor, associated with the regulation of the bronchomotor tone and airway inflammation.
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The nose contains three different types of epithelium; (1) the squamous epithelium in the vestibule, (2) the respiratory epithelium and (3) the special sense epithelium. The squamous epithelium of the vestibule is simply a portion of the skin that extends within the nostril. It does not enter into the present study. The respiratory epithelium takes in the largest portion of the nose. It extends from the squamous epithelium anteriorly to the squamous epithelium of the nasopharynx posteriorly and from the floor of the nose up to the olfactory area. The respiratory epithelium is pseudo-stratified, ciliated columnar in type (figs. 1 and 2). The superficial layer is composed of long columnar cells, each of which is surmounted by a tuft of rather long cilia. It contains many goblet cells. There are usually from three to five layers of these. All of the epithelial cells, including the surface columnar cells, extend
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Respiratory Mucosa
Mucociliary clearance
Respiratory tract
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The respiratory epithelium lines the conducting airways and functions as a selective barrier interposed between
external environment and human body. It is exposed to various aggressive factors such as viral and bacterial
microorganisms, or cigarette smoke and other inhaled noxious substances. The normal airway epithelium has its own
mechanisms that maintain the integrity of the epithelial barrier and it is relatively refractory to a number of apoptotic
stimuli. The up to date data about apoptosis in normal airway epithelium are limited, especially regarding the regulatory
factors of this process. The current knowledge concerning the airway epithelium apoptosis regulation needs to be further
studied by exploring the Bcl-2 superfamily members, Zn, p21, or peroxiredoxine V and pirine.
Respiratory tract
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Normal tracheal mucociliary clearance is the key to maintaining the health and defense of respiratory airway. Therefore the present of cilia and mucous blanket are important for tracheal epithelium to function effectively. In the present study, we prepared a tissue engineered respiratory epithelium construct (TEREC) made of autologous respiratory epithelium cells, fibroblast and fibrin from sheep owns blood which replaced a created tracheal mucosal defect. Scanning electron microscopy (SEM) showed encouraging result where immature cilia were present on the surface of TEREC. This result indicates that engineered respiratory epithelium was able to function as normal tissue.
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Despite an efficient defence system, the airway surface epithelium, in permanent contact with the external milieu, is frequently injured by inhaled pollutants, microorganisms and viruses. The response of the airway surface epithelium to an acute injury includes a succession of cellular events varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even to complete denudation of the basement membrane. The epithelium has then to repair and regenerate to restore its functions. The in vivo study of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to reconstitute a functional respiratory epithelium after several weeks. Humanised tracheal xenograft models have been developed in immunodeficient nude and severe combined immunodeficient (SCID) mice in order to mimic the natural regeneration process of the human airway epithelium and to analyse the cellular and molecular events involved during the different steps of airway epithelial reconstitution. These models represent very powerful tools for analysing the modulation of the biological functions of the epithelium during its regeneration. They are also very useful for identifying stem/progenitor cells of the human airway epithelium. A better knowledge of the mechanisms involved in airway epithelium regeneration, as well as the characterisation of the epithelial stem and progenitor cells, may pave the way to regenerative therapeutics, allowing the reconstitution of a functional airway epithelium in numerous respiratory diseases, such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis and bronchiolitis.
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The airways are lined with a film of fluid ∼10 μm deep that acts as the first line of defense against inhaled pathogens, dirt, and noxious vapors. Transepithelial fluid movements driven by active transepithelial ion transport serve to regulate the depth of this "airway surface liquid". In the larger airways, a mucus gel derived from both glands and surface epithelium entraps inhaled particles, which are then removed by the coordinated beating of cilia. Both glands and epithelium secrete a wide variety of antimicrobial and other protective substances in addition to mucins. Substances released across the basolateral surface of the epithelium attract leukocytes and influence neighboring tissues. Here, after reviewing the basic structure of mammalian airway epithelium, I discuss its various defensive functions and how they are altered in airway disease.
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