Mucus in respiratory airways
Mucus in airways acts with ciliary beating to keep clear the airways, giving rise to the mucociliary ascendant.
Mucus is very complex in its composition, is mainly produced by goblet cells and serous glands in bronchi wall. The main protein in mucus is the mucoprotein. In pathological hypersecreting states as in asthma and COPD, occurs changes in phenotypic expression with hyperplasia of goblet cells and hypertrophy of serous glands. The excess of mucus causes plugging in the airways and impacts not only lung function, but causes morbidity even mortality.
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The mucus is a complex mixture of proteins, lipids, water, and electrolytes that, under normal conditions, maintains the moisture of the airway epithelium. It allows the air to be conditioned adhering particles which bypasses upper airways. The main protein of the mucus is the mucin.
Taken from Lafitte, in
It is produced by goblet, mucous, and serous cells ( Flicker JH et al, 2008 ) and stored until a secretory signal is given. The mucus secretion may be stimulated by mediators produced by macrophages, lymphocytes, and epithelium.
Goblet cell in H/E staining
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Goblet secrets mucin, suspended in a solution of electrolytes.
Goblet cells, serous glands in bronchi. Hematoxyllin and eosine staining
The proteic component is assembled from amino acids on ribosomes, then it move up trough endoplasmic reticulum to enter to the Golgi saccules. In this Golgi saccules simple sugars enter and combine with proteins by glycosylation and sulfate is added. The saccules of glycoprotein are transformed and hydrated into globules of mucus. Finally the mucin globules move toward the cell apex for subsequent release from the cell into the lumen.
Drawing of a Goblet cell, depicting the different structures giving place to mucoprotein.
From Neutra and Leblond, taken with modifications of
Secretory cells release not only mucin but a variety of antimicrobial molecules such as lisozyme, defensins, and IgA, immunomodulatory molecules such as the so called secretoglobins and cytokines, and recently described protective molecules such as trefoil proteins and heregulin in constitutive and inducible way; all of these molecules can become incorporated into mucus (Fahy JV & Dickey BF, 2010 )
Function of mucus
The mucus-lined nasal and sinus passages collect pollen, dust, dirt, fungal spores, and other particulates from the air. Mucus production is balanced with the sweeping action of ciliated epithelium, which facilitates drainage and particulate removal.
The consistency of mucus (a complex of water, sugar, lipids, and protein) can change from a planar structure to a globular structure that is not as effective at covering mucosal membranes and collecting particulates.
Mucins are large glycoproteins and can be divided into membrane-bound and secreted mucins. There are nine membrane-bound (MUC1, MUC3A, MUC3B, MUC4, MUC12, MUC13, MUC16, MUC17 and MUC20) and six secreted mucins (MUC2, MUC5B, MUC5AC, MUC6, MUC7 and MUC19) have been described.
The secreted mucins can be further subdivided into gel-forming (MUC2, MUC5B, MUC5AC, MUC6 and MUC19) and non-gel-forming mucins (MUC7). The gel-forming mucins constitute the main structural component of the mucus gel protecting the underlying epithelia. (Lidell ME and Hansson GC, 2006 )
Mucus hypersecretion and phenotypical changes
Airway mucus hypersecretion is a key feature in the pathophysiology of chronic respiratory diseases both reversible and non-reversible like asthma and chronic obstructive pulmonary disease (COPD). The mucus hypersecretion is associated with phenotypic changes in the airways, notably, with increasing in the number of surface epithelial goblet cells (hyperplasia) and in the size of the submucosal glands (hypertrophy).
The phenomena of hyperplasia and hypertrophy are associated with increased production of mucin, the gel-forming component of mucus. In this way, the excessive mucus production contributes to morbidity and mortality in many patients, particularly in those with more severe disease ( Lai H & Rogers DF, 2010 )
Biofilm in mucus
Biofilms play an important role in otitis media, sinusitis, chronic cholesteatomatous otitis media, tonsillitis and adenoiditis, thus demonstrating that adenoidectomy may be helpful to children suffering from such a morbid conditions. It is presently estimated that biofilm formation is involved in at least 60% of all chronic and/or recurrent infections. In addition, 30% of the exudates developing in the course of otitis media has shown to be positive for the presence of biofilms; likewise biofilms have been found in tonsillar crypts and in odontostomatologic infections as well. Studies have been carried out on both the use and the efficacy of N-acetylcysteine (NAC) in biofilm breakdown. It has been shown that NAC, used at different concentrations, is able to reduce bacterial adhesion in several anatomical districts (Legnani D, 2009).
Mucus hypersecretion in COPD
Neutrophils are the key cells in pathologies such as the called chronic obstructive pulmonary disease (COPD); there is emerging evidence that these neutrophils play a key role in Epidermal Growth Factor Receptor (EGFR)-mediated mucin production through releasing tumor necrosis factor-alpha (TNF-α) and hence inducing EGFR expression. Moreover, the differentiation of the mucus cells as well as secretion of the mucus from airway glands are induced by neutrophil elastase.
Nevertheless, by entrapping and removing foreign materials, the mucus forms a basic defense system of the respiratory system; is easier for the lung cleaning to eliminate particles by mucociliary clearance instead of phagocytic process by the alveolar macrophages.
In the large airways, mucus hypersecretion causes coughing and sputum production. In the peripheral airways, because of the smaller diameter, the formed mucus plugs are difficult to remove and may block the peripheral airway completely. This, in turn, may result in gas trapping with increased total lung capacity (TLC) and decreased forced vital capacity (FVC). In COPD, the mucus hypersecretion is so then associated with decline in functional class, disease exacerbation (Poole and Black, 2003), accelerated decline in FEV1 and inflammatory cell infiltration ( Wedzicha and Donaldson 2003).
Moreover, the remaining sputum hinders the accessibility of inhaled medication to the peripheral airways. Therefore the mucus clearance and sterility maintenance are of importance in COPD.
There is a large number of medications available that are meant to change the properties of airway secretion or block its production or release, or both. The so called mucolytics are responsible for the disruption of the mucous gel, generally by altering the degree of the cross-linking or the interactions between molecules in the gel. Mucolytics include compounds as N-acetylcysteine (NAC) and related compounds, dornase–α, F-actin, de-polymerizing agents and nondestructive mucolytics, like hypertonic saline and oligosaccharide agents and were previously reviewed (King and Rubin, 2002 ).
Mucus hypersecretion in asthma
The secretion of tenacious mucus forming plugs is a hallmark of asthma, and it may results in variable degrees of severity of the disease. It is the result of the inflammatory process in the small airways.
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Asthmatic airways show both a hyperplasia and metaplasia of goblet cells, all of these cells are mucin-producing in the epithelium. The hyperplasia refers to augmented numbers of goblet cells in larger airways, while metaplasia refers to the appearance of these cells in smaller airways where they normally are not seen. With the augmented number of mucin-producing and secreting cells, there is a simultaneous hypersecretion of mucin which characterizes asthma.
A major regulator of airway mucin secretion in both in vitro and in vivo studies has been shown to be MARCKS (myristoylated alanine-rich C kinase substrate) protein, a ubiquitous substrate of protein kinase C (PKC) at a cellular level (Green TD et al, 2011 )
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