ChemInform Abstract: The Macrostructure of Mucus Glycoproteins in Solution

ChemInform ◽  
2010 ◽  
Vol 22 (40) ◽  
pp. no-no
Author(s):  
S. E. HARDING
Keyword(s):  
1979 ◽  
Vol 7 (5) ◽  
pp. 434-442 ◽  
Author(s):  
T C Medici ◽  
P Radielovic

The result of chemical analysis of the bronchial secretion is simple; up to 95% of the secretion is made up of water, and up to 5% is composed of ash, protein, carbohydrate, lipid, nitrogen and desoxyribonucleic acid. More complicated is the question of how bronchial secretion is formed and of which active biological components it is composed. Bronchial secretion is the result of the different processes, secretion, transudation, exudation and exfoliation from a highly differentiated bronchial mucosa. To those substances secreted belong, amongst others, constituents important for the flow properties and the transportability of the secretion: the bronchial mucus glycoproteins and water. The bronchial glycoproteins are the most important group, constituting 50–80% of the macromolecules. They are formed and secreted by the bronchial mucosa. The synthesis and secretion of bronchial glycoproteins are influenced by drugs in different ways. Beta-adrenergic stimulants do not alter these processes in in vitro studies on human glands, although an increase in mucus of glycoprotein production has been demonstrated in animal experiments and indirectly in man. Cyclic adenosine monophosphate and the methylxanthines stimulate mucus glycoprotein production, anticholinergic agents reduce but do not completely supress this process. Anti-allergic agents do not alter the production of bronchial glycoproteins with the exception of the corticosteroids which partially inhibit the synthesis and secretion. Neither expectorants nor mucolytic agents influence the production of mucus glycoproteins in human bronchial glands as opposed to animal experiments, in which these compounds produce an increase in the output of the bronchial fluid. Water constitutes 95% of the bronchial secretion and the water content considerably influences mucociliary function. An osmotic gradient, the result of active sodium and chloride ion transport across the bronchial epithelium, ensures on the one hand that water diffuses through epithelium on to the epithelial surface where it forms the serous sol layer in which the cilia beat. On the other hand water is probably transported in the same way across the mucosal glands where it mixes with the extremely hydrophilic mucus glycoproteins. The ion and water transport is influenced by drugs. Acetylcholine, histamine and terbutaline stimulate the ion and thereby water transport. Atropine, diphenylhydramine, an H1-antagonist, propranolol, a beta-blocker andfurosemide inhibit these transport mechanisms. Whether ketotifen, a new antihistaminic drug used in the treatment of bronchial asthma, will affect these processes, decreasing the water content of bronchial mucus, remains to be seen.


1983 ◽  
Vol 213 (2) ◽  
pp. 427-435 ◽  
Author(s):  
I Carlstedt ◽  
H Lindgren ◽  
J K Sheehan

Human cervical-mucus glycoproteins (mucins) were extracted with 6 M-guanidinium chloride in the presence of proteinase inhibitors and purified by isopycnic density-gradient centrifugation. The whole mucins (Mr approx. 10 × 10(6] were degraded into ‘subunits’ (Mr approx. 2 × 10(6] by reduction of disulphide bonds. Trypsin digestion of the ‘subunits’ produced glycopeptides with Mr approx. 380000, which appear to be rod-like with a length of approx. 105 nm. The relationship between the radius of gyration and the Mr value obtained by light-scattering for whole mucins, ‘subunits’ and ‘domains’ suggest that cervical-mucus glycoproteins are linear flexible macromolecules composed of, on the average, four or five ‘domains’/subunit and four subunits/whole mucin macromolecule. The shape-dependent particle scattering function for the whole mucins and the ‘subunits’ are in accordance with that of a linear flexible chain. No evidence for a branched or a star-like structure was found. A tentative model for cervical mucins is proposed.


1991 ◽  
Vol 274 (1) ◽  
pp. 293-296 ◽  
Author(s):  
J K Sheehan ◽  
R P Boot-Handford ◽  
E Chantler ◽  
I Carlstedt ◽  
D J Thornton

Polyclonal antibodies were raised in rabbits towards reduced subunits of human cervical mucus glycoproteins. The reduced subunits almost completely inhibited the antiserum, whereas the intact mucins and the heavily glycosylated fragments obtained after digestion of reduced subunits with trypsin (T-domains) caused only partial inhibition. Periodate oxidation of intact mucins, reduced subunits and T-domains caused no effect on the antibody response, and fragments obtained by more extensive proteolysis of the reduced subunits (P-domains) showed no inhibitory activity. By using electron microscopy, antibodies from T-domain-adsorbed antisera were revealed as bound to cervical mucin reduced subunits, either directly or with colloidal gold-Protein A. Binding sites (100-150 nm apart) were observed at the ends and at internal positions of the reduced subunits. We conclude that the antibodies do not recognize carbohydrate structures but are directed to two kinds of protein epitopes, one shared by whole mucins, reduced subunits and T-domains, and the other specific to the reduced subunit fragment. The latter epitopes are ‘cryptic’ and are probably shielded within folded protein domains stabilized by disulphide bonds. Human bronchial, cervical, gastric and salivary mucus glycoproteins share some of these cryptic epitopes.


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