Role of Airway Epithelial Cells Airway Epithelium as a Physical Barrier - Essay Example

Asthma Tutor Institution Course Date Asthma Introduction The bronchial epithelium is continually exposed to a variety of environmental substances found in inhaled air, entailing noxious gases as well as natural and anthropogenic particles, like gas and particulates from tobacco smoke, car emissions, animal dander, pathogens and pollens. As an entirely differentiated pseudostratified mucociliary epithelium, bronchial epithelium defends the lung’s internal environment from these substances through developing physical barrier entailing adhesive complexes and chemical barricade entailing discharge of mucus which ensnares inhaled substances that are then cleared by mucociliary escalator. It is through the efficiency of these barriers that majority atmospheric challenges are hugely surmounted without the requirement to form an inflammatory reaction. In addition, bronchial epithelium plays a significant function surveillance of the immune system and suitable stimulation of immune effector cells along with antigen presenting cells due to presence of dangerous signals and pathogens. Airway epithelium control both adaptive and innate immunity via secretion of functional molecules together with physical interrelations with immune system’s cells. Therefore, the airway epithelium has a core function of regulating innate immunity and tissue homeostasis. Role of airway epithelial cells Airway epithelium as a physical barrier The epithelium airway acts as the interface between the lungs and the inhaled air. It develops a multifaceted physicochemical barricade complemented by mucocilliary escalator to offer protection against inhaled antigens. Epithelial cells cover the entire surface that is in contact with air and are the core constituent to the physical barricade. They are connected to neighbor through cell to cell junctions, entailing tight junctions, gap junctions, desmosomes and adherens junctions. These structures create an effective and impermeable mechanical barricade and permit maintenance of ionic gradient the directional discharge of several secretions. Amid cell to cell junctions, tight junctions are the most significant for the maintenance of epithelial integrity and they compromise a sequence of interacting receptors and proteins which ensure the impermeability of the barricade and also enhance communication amid adjacent cells. In addition, they control intercellular transport (Roche et al, 2010). Situated below tight junctions , adheres junctions offer significant adhesive contacts amid neighboring epithelial cells whilst gap junctions are distinctive cell to cell conduits that permit diffusion of minute metabolites, ions and second messengers amid neighboring cells. Desmosomes are intercellular intersections that offer strong adhesion amid cell and create adhesive bonds within a network that mechanically support tissues. Cell to cell junctions operate as an obstacle to pathogen entry and distribution into airway submucosa. Therefore, merely via their physical existence along with the network they develop at the airway mucosa’s surface, epithelial cells signify a crucial and efficient frontline defense against invasion by virus and pathogens. The mucus on the surface of airway epithelium offers additional defense of the mucosa through forming a semipermeable barricade that enhances the exchange of gases, water and nutrients and is impermeable to several pathogens. Additionally, it permits efficient lung clearance via mucociliary apparatus (Bergelson, 2009). Airway epithelium as an immunologic barrier The immunological barrier comprises of cellular and humoral constituents and operates to safeguard the interior surrounding of the body through suppressing or activating adaptive and innate immunity. Humoral constituent involves nonspecific discharge of immunoglobins whilst the cellular constituent entails regulatory and memory T cells, macrophages, mast cells, B cells, plasma cells and dendritic cells. The epithelial cells take part in humoral immunity passively transferring immunoglobins from lamina propria to luminal surface. They take part in cellular immunity through physical interaction with and discharging chemokines and cytokines that direct close by immune cells. Homeostasis in the airway is maintained through active repression of adaptive and innate immunity via the discharge of transforming growth factor beta and interleukin 10 by the regulatory T cells and dendritic cells. In addition, epithelial cells contribute to immune repression via the constitutive discharge of interleukin 10 (Bonfield et al, 2012). How Asthma perturbs the normal role of the airway epithelium and smooth muscle cells. Airway remodeling in Asthma The epithelial lining of the airway acts as a frontier protector against respiratory pathogen as a physical obstacle and via the mucociliary apparatus and also via its immunological purposes. Apart from its function of maintain a air conduit form and to the alveoli, airway epithelium is vital to the protection of lungs against invading pathogens, via the merged role of ciliated secretory and epithelial cells maintaining proficient mucociliary clearance and via a wide range of additional host protection mechanism. Airway epithelial cells play the role of regulating both adaptive and innate immunity by producing functional molecules and through physical interrelations with immune system’s cells. Stimulation of airway epithelium leads to instant host protection reactions that entail production of anti pathogenic substance and proinflammatory cytokines that recruit and stimulate additional mucosal inherent immune cells and instigate adaptive immunity’s mechanisms (Brewster et al, 2011). The bronchial epithelial lining acts a barrier to external environment and is fundamental in the defense of the lung’s interior environment. The bronchial epithelium operates within the epithelial-mesenchymal trophic unit abbreviated as EMT in controlling the local atmosphere and assisting in maintaining tissue homeostasis. Nevertheless, in people with asthma, continual disturbance of these mechanisms of homeostasis results to modifications in the configuration of the airways, referred to as remodeling. Epithelium injury plays a pivotal role function in propelling remodeling of the airway. The vulnerability of the epithelium to environmental injury and stress along combine with damaged repair responses leads to the production of signals which act upon the underlying mesenchyme propagating and amplifying inflammatory as well as remodeling responses within the submucosa (Holgate, &Davies, 2012). Several confronts to epithelium, entailing allergens, environmental pollutants , mechanical forces, cigarette smoke and pathogens can stimulate the epithelium to produce mediators , which may be decoded into remodeling reactions by mesenchyme. Holgate (2011) notes that there are numerous significant remodeling mediators such as transforming growth factor beta, which is usually discharged from repairing or damaged epithelium or due to reaction to inflammatory mediators like Interleukin 13. The bronchial epithelium plays a pivotal role in providing immunological, physical and chemical obstacles to the air breathed from the environment. These obstacles acts in maintaining the homeostasis of the tissues, but when they are under compromise, the immunological barrier is activated so as to fend the lung’s internal environment. This results to a heightened response which have the capability of becoming pathological in case of constant activation. Therefore, a fast renovation is fundamental for the reinstatement of normal tissues homeostasis (Holgate, 2011). Epithelial injury and repair When the epithelial is injured, the procedure of repairing the damage takes place in a sequence of phases. The instant response entails stimulation of cell relocation resulting to the development of a provisional obstacle. The epithelial cells start migrating in reaction to growth factors, like epidermal growth factor of transforming growth factor beta, via going through an epithelial to mesenchyma transition marked by down regulation of the tight junctions as well as amplified expression of extracellular matrix and matrix metalloproteases. When airway epithelial cells are activated, the underlying assuaged fibrolast sheath reacts to epithelial damage by the production and deposition of a temporary matrix that assists close the provisional barricade whilst the airway epithelium is under compromise. This entails amplified propagation fibroblasts and the differentiation of these fibroblasts into myofibroblasts. These two processes are seen in asthma (Swindle et al, 2009). Following the immediate formation of a barrier, epithelial cells split so as to reinstate the lost cells and thus must go through differentiation. This originally entails differentiation of the goblet cells permitting reinstatement of secretory role, since the secretions offer further defense to airways. After this process, ciliogenesis takes place so as to reinstate mucociliary clearance. As epithelium goes back to usual function, the temporary matrix deposited in the early phases should be remolded and eradicated to reinstate normal architecture of the tissue. In this procedure, the myofibroblasts must go through apoptosis reinstate the submucous fibroblast to normal number (Swindle et al 2009). In asthma, there is abnormal epithelial damage and repair. There is increased vulnerability to injury along with unusual repair responses, entailing amplified expression of cyclidependent kinase inhibitor. Brewster et ( 2011) note that in addition, in asthmatic people, airway epithelium has dysregulated reinstating responses and usually take longer in the repair of mechanically induced injuries. They also undergo a more pervasive epithelial mesenchyme trophic unit in reaction to transforming growth factor beta than in people without asthma. Asthma and dsyregulation of epithelial barriers The bronchial epithelial barricade is functionally and structurally altered in asthmatic individuals. The most consist and notable characteristic of the modified epithelium is amplification in expression of mucin gene and the amount of goblet cells within the epithelium. The amplifications are linked to amplified expression of epidermal growth factor receptor as well as the action of T- helper 2 cytokines, entailing interleukin 9 and interleukin 13. Epithelial shedding and epithelial fragility are common in asthmatic individuals. Epithelial shedding usually entails loss of the columnar epithelial cells, leading to exposure of regions of basal cell on the epithelium’s apical surface. In addition, the physical barricade of asthmatic bronchial epithelium is interrupted, with loss of proteins of the tight junctions, a decrease in proteins of the adherens junctions and a decrease in the length of the desmosome (Holgate, 2011). Asthmatic airway epithelium have increased sensitivity and permeability to atmospheric challenges as well as increased vulnerability to oxidant trauma. In addition, asthmatic epithelial cells have enlarged inflammatory response following mechanical wounding or exposure to respiratory syncytial virus and particulate matter. Alteration of the airway epithelium in asthma entail epithelial shedding, damage of ciliated cells, hyperplasia of globlet cell , up regulation of release of growth factor and increased expression of receptors like epidermal growth factor receptors (Laitinen et al, 2010). According to Nadel (2013) submucosal gland hyperplasia and goblet cell hyperlapsia are observed in airways of individuals with asthma. Functional effects of these anomalies mainly lead to amplified production of sputum, narrowing of the airway as a result of secretion of sputum and amplified thickness of the wall of the airway. The undamaged airway epithelium usually offers a physical defense barricade against inhaled minute particles like allergens and pathogens. The damage of the epithelial surface along with the consequential denudation of basement membrane might reduce this defensive impact and raise the susceptibility for allergic affront to the airway (Nadel, 2013). Increased smooth muscle mass The excessive narrowing of airway that can result to severe breath shortness and respiratory failure in asthmatic patients is as result of contraction of bands of the smooth muscles found within the walls of medium and large sized conducting airways within the lung. The smooth muscle of the respiratory airway is the vital effector adjusting airway tone. Within asthmatic airways, the mass of smooth muscle is amplified as a result of a synchronized in the number (hyperplasia) and size (Hypertrophy) of smooth muscle cells of the airway. Significantly, asthmatic smooth muscle cells take on proliferative and secretory phenotype and may also move to subepithelial region of asthmatic airways. The cells of smooth muscle actively take part in the remodeling and inflammatory procedures via their discharge of the proinflammatory cytokines, extracellular matrix proteins and chemokines, and thus, might lead to asthma pathogenesis (Johnson 2010). The immigration of cells of the smooth muscles is a common feature of remodeling of the airway. Chemokines have the capability of stimulating migration of cells of the smooth muscles and increasing their contractility inside the cell, incriminating a further avenue that might considerably lead to obstruction of overall airflow in asthmatic patients. Johnson (2010) claims that cell migration is partly responsible for pathogenesis of smooth muscles of airways hyperlapsia as well as remodeling in asthma. In addition, the movement to cells of the smooth muscle towards the airway’s lumen underlies the look of myofibroblasts within the subepithelium of asthmatic airway. Since myofibroblasts act as a source of the extracellular matrix proteins such as fibronectin, tenascin and collagen, all of which are found in subepithelium of asthmatic patients, the migration of myofibroblasts to subepithelium might be the major factor in formation of subepithelial fibrosis (Johnson, R, 2010). Conclusion The epithelium airway functions as the frontline protector against respiratory pathogens as a physical barrier and via its immunological role. Apart from its function of maintain the flow of air from and to the lungs, airway epithelium plays a significant role in defending the lung from damage by pathogens, via the merged function of secretory and epithelial cells maintain effective mucociliary clearance and via a wide range of host protection mechanism. However, asthma causes an alteration in the structure and operation of the airway epithelium. These changes entail thickening of the airway, myofibroblast hyperplasia, subepithelial fibrosis as well as smooth muscle cell hypertrophy and hyperplasia. These changes occur as a response to continuing tissue damage caused by allergens, inhaled particulates and infectious agents. Epithelial injury involves loss of integrity of the airway epithelium, interruption of tight junctions and impairment of the function of the epithelium as a barrier. Bibliography Roche, W., Montefort, S., Baker, J, & Holgate, T., 2010, Cell adhesion molecules and the bronchial epithelium. Amrican Review of Respiratory Diseases, 148, 79- 82. Bergelson, J., 2009. Intercellular junctional proteins as receptors and barriers to virus infection and spread. Cell Host Microbe 5:517-521. Bonfield, L., Konstan, W., & Burfeind, P., 2012, Normal bronchial epithelial cells constitutively produce the anti-inflammatory cytokine interleukin-10, which is downregulated in cystic fibrosis. American Journal of Respiratory Cell and Molecular Biology, 13, 257–261 Swindle, J., Collins E., & Davies, E, 2009, Breakdown in epithelial barrier function in patients with asthma: identification of novel therapeutic approaches. Journal of Allergy and Clinical Immunology, 124, 23–34 Brewster, E., Howarth, H., & Djukanovic R., 2011, Myofibroblasts and subepithelial fibrosis in bronchial asthma. American Journal of Respiratory Cell and Molecular Biology, 3, 507–511. Laitinen , A., Heino, M., & Kava, T., 2010, Damage of the airway epithelium and bronchial reactivity in patients with asthma. American Review of Respiratory Diseases, 131:599–606. Holgate, T, 2011, Pathophysiology of asthma: what has our current understanding taught us about new therapeutic approaches? Journal of Allergy and Clinical Immunology, 128, 495–505 Nadel, A, 2013, Mucous hypersecretion and relationship to cough. Pulmonary Pharmacology and Therapeutics Journal, 26, 510–513 Holgate, T, & Davies, E., 2012, Airway inflammation and remodelling in asthma—cause and effect? The Immunologis, 8, 131–135. Johnson, R, 2010, Role of human airway smooth muscle in altered extracellular matrix production in asthma. Clinical and Experimental Pharmacology and Physiology, 28, 233–236 Read More