Mucus in respiratory airways

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  • 8/6/2019 Mucus in respiratory airways


    Mucus in respiratory airways.

    AbstractMucus in respiratory airways is produced by several sources, mainly goblet cells, it has complex gene

    regulation for its production and its alterations are mostly present in obstructive reversible and non-

    reversible respiratory disease, such as in COPD and asthma. It is related with the formation of biofilmand in this way allows bacterial infection.


    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.

    MucinImagen credit:

    Taken from Lafitte, in
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    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 stainingCredit of image Goblet secrets mucin, suspended in a solution of electrolytes.

    Goblet cells, serous glands in bronchi. Hematoxyllin and eosine stainingImage credit:
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    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 aretransformed 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
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    Function of mucus

    The mucus-lined nasal and sinus passages collect pollen, dust, dirt, fungal spores, and other particulates fromthe air. Mucus production is balanced with the sweeping action of ciliated epithelium, which facilitates drainageand particulate removal.

    Different particles in air: molds, polen dust mites.

    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


    (Helms and Miller, 2006).


    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, MUC17and MUC20) and six secreted mucins (MUC2, MUC5B, MUC5AC, MUC6, MUC7 and MUC19) have

    been described.
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    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 HanssonGC, 2006)

    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 thecourse 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 severalanatomical districts.

    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 FactorReceptor (EGFR)-mediated mucin production through releasing tumor necrosis factor-alpha (TNF-)

    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 isso 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 thedisruption 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
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    compounds, dornase, 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 variabledegrees of severity of the disease. It is the result of the inflammatory process in the small airways.

    Credit of image:

    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 asimultaneous 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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    Ficker JH. [Physiology and pathophysiology of bronchial secretion]. Pneumologie. 2008 Mar;62

    Suppl 1:S11-S3

    Green TD, Crews AL, Park J, Fang S, Adler KB. Regulation of mucin secretion and inflammation

    in asthma: A role for MARCKS protein? Biochim Biophys Acta. 2011 Jan 31. [Epub ahead of

    print] PubMed PMID: 1281703.

    Helms S, Miller A. Natural treatment of chronic rhinosinusitis. Altern Med Rev. 2006

    Sep;11(3):196-207. Review. PubMed PMID: 17217321.

    King M, Rubin BK. Pharmacological approaches to discovery and development of new mucolyticagents. Adv Drug Deliv Rev. 2002 Dec 5;54(11):1475-


    Lidell ME, Hansson GC. Cleavage in the GDPH sequence of the C-terminal cysteine-rich part ofthe human MUC5AC mucin. Biochem J. 2006 Oct 1;399(1):121-9. PubMed PMID: 16787389. Full text in

    Neutra M, Leblond CP. The Golgi apparatus. Sci. Am. 1969; 220: 100107

    Pintucci JP, Corno S, Garotta M. Biofilms and infections of the upper respiratory tract. Eur Rev

    Med Pharmacol Sci. 2010 Aug;14(8):683-90. PubMed PMID: 20707288.

    Poole PJ, Black PN. Preventing exacerbations of chronic bronchitis and COPD: therapeutic

    potential of mucolytic agents. Am J Respir Med. 2003;2(5):367-370

    Sadowska AM, Verbraecken J, Darquennes K, De Backer WA. Role of N-acetylcysteine in the

    management of COPD. Int J Chron Obstruct Pulmon Dis. 2006;1(4):425-34. Review. PubMed

    PMID: 18044098;

    Wedzicha JA, Donaldson GC. Exacerbations of chronic obstructive pulmonary disease. RespirCare. 2003 Dec;48(12):1204-13; discussion 1213-5. Review. PubMed PMID: 14651761.
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    Alejandro Melo-Florin MD

    Internal Medicine Specialist

    Pontificia Universidad JaverianaBogot D.C. Colombia

    Competing Interests: Working with pharmaceutical

    manufacturere-mail: [email protected]