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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.

Introduction

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

http://worldtrip.bloguez.com/worldtrip/1515071/Mucin
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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

http://www.vivo.colostate.edu/hbooks/pathphys/misc_topics/goblets.html Goblet secrets mucin, suspended in a solution of electrolytes.

Goblet cells, serous glands in bronchi. Hematoxyllin and eosine stainingImage credit:

http://www.mc.vanderbilt.edu/histology/labmanual2002/labsection2/Respiratory03.htm
http://www.ncbi.nlm.nih.gov/pubmed/18317975http://www.ncbi.nlm.nih.gov/pubmed/18317975http://www.ncbi.nlm.nih.gov/pubmed/18317975http://www.vivo.colostate.edu/hbooks/pathphys/misc_topics/goblets.htmlhttp://www.vivo.colostate.edu/hbooks/pathphys/misc_topics/goblets.htmlhttp://www.mc.vanderbilt.edu/histology/labmanual2002/labsection2/Respiratory03.htmhttp://www.mc.vanderbilt.edu/histology/labmanual2002/labsection2/Respiratory03.htmhttp://knol.google.com/k/-/-/3sktw3ldc86j2/sgxz2p/imagesca4cf48q.jpghttp://knol.google.com/k/-/-/3sktw3ldc86j2/sgxz2p/goblethe.jpghttp://knol.google.com/k/-/-/3sktw3ldc86j2/sgxz2p/imagesca4cf48q.jpghttp://knol.google.com/k/-/-/3sktw3ldc86j2/sgxz2p/goblethe.jpghttp://www.mc.vanderbilt.edu/histology/labmanual2002/labsection2/Respiratory03.htmhttp://www.vivo.colostate.edu/hbooks/pathphys/misc_topics/goblets.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/18317975


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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 ofhttp://www.comprehensivephysiology.com/WileyCDA/CompPhysArticle/refId-cp090116.html
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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

particulates.

(Helms and Miller, 2006).

Mucins

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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570170/pdf/bj3990121.pdfhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570170/pdf/bj3990121.pdfhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570170/pdf/bj3990121.pdfhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570170/pdf/bj3990121.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/14719989http://www.ncbi.nlm.nih.gov/pubmed/14719989http://www.rcjournal.com/contents/12.03/12.03.1204.pdfhttp://www.rcjournal.com/contents/12.03/12.03.1204.pdfhttp://www.rcjournal.com/contents/12.03/12.03.1204.pdfhttp://www.rcjournal.com/contents/12.03/12.03.1204.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/14719989http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570170/pdf/bj3990121.pdfhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1570170/pdf/bj3990121.pdf


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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:

http://littledoctors.wordpress.com/2011/01/12/chronic-obstructive-pulmonary-disease-bronchial-asthma/

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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Alejandro Melo-Florin MD

Internal Medicine Specialist

Pontificia Universidad JaverianaBogot D.C. Colombia

Competing Interests: Working with pharmaceutical

manufacturere-mail: [email protected]