Mucus is our first barrier against the outside world. It is found on the luminal side of most epithelial surfaces, for instance the mouth, respiratory tract, gastrointestinal tract, urogenital tract, joint surfaces and corneal surfaces. However, we are largely unaware of the importance of our mucus until something goes wrong in these systems. For example when we have a cold or inhale some dust or pollen, we become aware of our own mucus as an unpleasant, slimy and messy nuisance; or when someone swallows something dangerous like a safety pin or a nail, in most cases it passes through the stomach and gut causing very little damage because of the secretion of mucus which protects and lubricates the epithelial surfaces of the tract. So what is this unpleasant hut vital nuisance?

Mucus is a viscoelastic gel-like material. It has been used to describe the coating and/or lining layers of vertebrates (e.g. fish, mammals) and invertebrates (e.g. coelomates, molluscs) (Rose, 1992). As noted earlier, in mammals the term mucus is restricted to the material covering the epithelial surfaces and providing an interface between the external environment and the epithelial layers. In vertebrates, this interface provides lubrication, maintenance of tissue hydration, and cytoprotection against proteases - a group of enzymes that break down the bonds amoung aminoacids - pH extremes, chemical irritants, and biological agents. Whereas invertebrate mucus has additional biological functions, like navigation, locomotion, and structural support (Denny, 1989). In the human both, the importance of these biological functions may vary depending on the location of the mucus: for example, in the respiratory tract, to clear the airways of inhaled particles: in the eyes, to prevent corneal surfaces from drying: in the reproductive tract, to protect the uterine cavity and control the survival and penetrability of the spermatozoa. However, there is one important function common to all systems, namely the maintenance of the mucosal water balance.

The composition of mucus

It is important to know something about the biological composition of mucus. In humans, this viscoelastic gel usually contains more than 90% water, 0.5-5% high molecular weight glycoproteins, termed mucins, and also a large number of other components such as electrolytes, lipids, plasma proteins and nucleic acids. Mucins are extremely large and heavily glycosylated molecules that consist primarily of a non-globular, thread-like polypeptide backbone and 0-linked oligosaccharide side chains. Within the mucin producing cells the molecules are found, without water, within large membrane-bound granules that fill the upper part of the cell. It appears likely that the mucins are the major determinants of mucus behaviour, and non-mucin constituents such as DNA, lipids and proteins are, when present, likely to influence the properties of the gel (Carlstedt, 1988). However, acidic mucopolisaccharides and glycoproteins are the major macro- molecular components of mucus in other animals, such as marine snail mucus (Rose, 1992).

In general, the gel forming mucin macromolecules have an oligomeric structure and are assembled from subunits via disulphide bonds. They can be fragmented into subunits by reduction of these disulphide bonds (Thornton. 1995). On the basis of their sensitivity to proteases it is believed that mucins typically contain two different types of domains that are highly glycosylated regions (rich in serine and threonin) and ‘naked’ hydrophobic regions that have lower substitution with carbohydrates. Where when and how does such a complex substance get synthesized, assembled and secreted? And what can happen if the process goes wrong or gets out of balance?

In the gastrointestinal tract

One of the common places where mucus has many vital functions is the gastrointestinal tract. The main site of production of intestinal mucin is the goblet (mucous) cell. However; there is a small amount of mucus production in columnar cells (intestinal epithelial cell). Mucus secretion is probably under both neural and hormonal control. However, little is known about exocytosis in which the membrane of the granules fuses with the apical plasma membrane, thereby releasing its contents.

In this tract, mucus forms a protective layer between the epithelial surface and the luminal compartment, and has been indicated in the mechanical protection of the gastrointestinal epithelial cells from bile acids, pH extremes, digestive enzymes, biological agents such as bacteria, virus and parasites, and mechanical damage. Also, in the stomach, mucus provides a mixing and diffusion harrier which protects the stomach wall from the damaging effects of the secreted hydrochloric acid which plays a big part in the digestion of our food. Bicarbonate ions are secreted into the unstirred mucus layer to help neutralize the acid and limit its harmful effects (Flemstrom, 1987). We are unaware of this function of mucus generally; however, when someone has a stomach or duodenal ulcer, or any types of gastritis, they have to take some anti- acidic drugs and so become aware of their neutralizing mucus blanket.

We know little about the involvement of gastrointestinal mucus in disease. It is suggested that there is a selective loss of a ‘specific’ mucin subpopulation in ulcerative colitis which is an inflammatory intestinal disease (Podoisky & Isselbacher, 1984). Many recent studies indicate that mucins secreted by colorectal carcinoma are immunologically and biochemically different from those in normal colon and adenomatous colon in which there is epithelial benign tumour and/or tumours in the colorectum (Gendler eta1., 1990; lass et al., 1994). Moreover, it has been shown that some components of mucus can be employed as a marker for colonic carcinoma and pre-cancerous conditions (Guang & Abdulkalam. 1995).

In the respiratory tract

Another common place for mucus is the respiratory tract, where mucus is produced by submucosal glands and by goblet cells interspersed among the ciliated respiratory epithelial cells. The cilia are like tiny hairs and are very numerous on epithelial cells of the upper respiratory tract. There maybe 250 or more cilia on the surface of a ciliated epithelial cell, arranged in regular rows. The ciliated epithelial cells, together with a thin mucus layer, constitute the mucociliary transport system designed to clear the airways from foreign particles such as dust, pollen, bacteria or other harmful particles. When we inhale these harmful particles into the lungs, a local stimulation of mucus secretion is evoked. The mucus blanket surrounds the particle and is moved by the cilia which beat in a rhythmical, wave-like manner into the trachea and from there it is swallowed to the gastrointestinal tract. In this propelling the gel towards the pharynx (the upper part of the trachea), the tips of the cilia interact with the mucus layer so that the energy can be passed from the cilia to the mucus blanket. If something goes wrong with the ciliated epithelium or the epithelium is depleted of mucus, this transport may not necessarily occur.

Although in healthy individuals goblet (mucous) cells represent on average 1/10 of ciliated cells, in a chronically obstructed airway (when diseases such as bronchitis, asthma, bronchorrhea and cystic fibrosis are present) the number of the goblet cells and of the submucosal glands increases markedly. In these particular diseases, hyperplasia of goblet cells, hypertrophy of submucosal glands and the hypersecretion of mucus are the prominent features of the pathological process. The most common inherited disease where mucus is very important is cystic fibrosis. This disease appears in about 1 in 2000 people born in Europe and America, although 1 in 20 people carry the defective gene. In this case mucus is stickier than normal and so the abnormally sticky mucus cannot be easily removed from the lungs. Instead of acting as the means for removing bacteria, the mucus becomes a breeding medium for them and the complications of the resulting infection ultimately lead to early death.

In the reproductive tract

Besides the gastrointestinal and respiratory tracts, mucus is very important also in the reproductive tract. The cervical canal, the entrance to the upper reproductive tract, is filled with mucus whose biological functions are to protect the genital tract from infection and to control the survival and penetrability of the spermatozoa (male germ cell). The amount and physical properties of mucus vary during the ovulatory cycle. At ovulation, when the woman produces ova from her ovary, there is an increased hydration of mucus which results in a watery secretion with high spermatozoal penetrability and low viscoelasticity (Wolf et al., 1978). In contrast, during the luteal phase, the second part of the menstrual cycle, the mucus is scant, contains less water and provides an effective barrier to the spermatozoa (Carlstedt et al., 1988). During pregnancy a large mucus plug blocks the cervical canal in order to protect the uterine cavity including the baby from any external effects. If the composition of the mucus changes during the early stages of the pregnancy, this mucus plug may become defective and the pregnancy may result in abortion or premature birth. It has been shown that high levels of cell-surface MUC1 (a mucin gene product) inhibit both cell-cell and cell-matrix adhesion that is important in human embryo implantation and this occurs in the mid-secretory phase of the menstrual cycle (Aplin & Hey, 1995). Moreover, the changing of mucus composition may be an important factor in infertility, because it controls the survival and penetrability of the spermatozoa. Also, there is the same significant alteration in the biochemical characteristics of the mucus in endometrial carcinoma.

Alterations in mucus composition

As mentioned earlier, there are some notable alterations in the biochemical characteristics of mucins in many diseases. For example, in chronic obstructive respiratory disease excess mucus is present in airways. In cancer, one frequently finds abnormal carbohydrate structures on mucins that can serve as surrogate markers for tumour progression. Also, mucin peptide epitopes that are normally covered with carbohydrates become uncovered and can serve as markers. Since membrane mucins can function as anti-cell adhesion molecules, and their over expression in cancer may facilitate tumour dissemination and therefore metastases. However, there is still a lot of work to be done to understand biosynthesis, secretion and functions of the mucus, especially mucins, in healthy people or in diseased conditions. How is it that mucus can change in response to environmental influences, bacterial attack, or hormonal balance? What is the relationship between mucus and the progression of cancer or such kind of life-threatening diseases? It is clear that mucus is susceptible to almost infinite and rapid modification. When we understand how this capability is employed and controlled, we may be one step nearer to controlling sonic life-threatening diseases, such as cystic fibrosis, cancer, or some abnormal conditions, like infertility and miscarriage.

As a conclusion we can say that mucus may appear a sticky, tiresome, messy nuisance hut it is obvious that a life without mucus would he extremely uncomfortable. It is a gift of the Creator to all living beings, and a miracle, many of whose wonderful mysteries remain to he discovered.

References

Aplin J.D. & HEY NA. (1995) ‘MUCl, Endometrium and Embryo Implantation’, Bioch, Soc. Trans., 23, pp. 826-31.

Carlstedt I. (1988) Mucus Gylcoproteins: Structure and Macromolecular Properties, Lund University Press, Lund,

Denny M.W, (1989) ‘Intervertebrate mucus secretions: functional alternatives to vertebrate paradigms’. Symp. Soc. Exp. hal. 43, p. 337.

Flemstrom (3. (1987) Physiology of Gastrointestinal Tract, Raven Press, New York, pp. 1011-29.

Gendler S.J., Lancaster C., Taylor-Papadimitriou J., Duhig T., Peat N., Burchell ,J.. Pemberton L., El-Nasir I .., Wilson D. (1990) ‘Molecular

cloning and expression of human tumour-associated polymorphic epithelial mucin’. .J Biol. Chem. 265, pp. 15286-93.

Guang Y.Y. & Abdulkalam MS. (1995) ‘A new monoclonal antibody, CMU1O, as a marker for colonic carcinoma and precancerous conditions’. Arch, Pathol. Lab. Med., 114, Mayc pp. 454-60.

Jass JR., Robertson A.M. (1994) ‘Colorectal mucin histochemistry in health and disease: a critical review’, Pathol. Int,. 44, pp.487-504.

Podolsky D. & Isselbacher K.J. (1984) Gastroenterology, 87, pp.99 1-8. Rose MC. (1992) ‘Mucins: structure, function, and role in pulmonary diseases’. The Am. Physiol. Soc., pp. L413-L429.

ThorntonD.J., Howard M., Devine P.L.,. Sheehan J.K. (1995) ‘Methods for separation and deglycosylation of mucin subunits’. Analytic Biochemistry. 227, pp.162-7.

Wolf DR Blasco L., Khan M.A., Litt M. (1978) , Fertil. Steril. 30, pp.l63-9,

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