Julia R Davies | PubMed Health

PubMed2002

Gastric MUC5AC and MUC6 are large oligomeric mucins that differ in size, glycosylation and tissue distribution.

Gastric MUC5AC and MUC6 mucins were studied using polyclonal antibodies. Immunohistochemistry showed MUC5AC to originate from the surface epithelium, whereas MUC6 was produced by the glands. Mucins from the surface epithelium or glands of corpus and antrum were purified using CsCl/4M guanidinium chloride density-gradient centrifugation. MUC5AC appeared as two distinct populations at 1.4 and 1.3 g/ml, whereas MUC6, which was enriched in the gland tissue, appeared at 1.45 g/ml. Reactivity with antibodies against the Le(b) structure (where Le represents the Lewis antigen) followed the MUC5AC distribution, whereas antibodies against the Le(y) structure and reactivity with the GlcNAc-selective Solanum tuberosum lectin coincided with MUC6, suggesting that the two mucins are glycosylated differently. Rate-zonal centrifugation of whole mucins and reduced subunits showed that both gastric MUC5AC and MUC6 are oligomeric glycoproteins composed of disulphide-bond linked subunits and that oligomeric MUC5AC was apparently smaller than MUC6. A heterogeneous population of 'low-density' MUC5AC mucins, which were smaller than the 'high-density' ones both before and after reduction, reacted with an antibody against a variable number tandem repeat sequence within MUC5AC, suggesting that they represent precursor forms of this mucin. Following ion-exchange HPLC, both MUC5AC and MUC6 appeared as several distinct populations, probably corresponding to 'glycoforms' of the mucins, the most highly charged of which were found in the gland tissue.

Centrifugation, Density Gradient↗

PubMed2002

Respiratory tract mucins: structure and expression patterns.

Goblet cells produce mainly MUC5AC, but also MUC5B and some MUC2 in apparently 'irritated' airways. MUC5B dominates in the submucosal glands although a little MUC5AC and MUC7 are usually present. MUC4 originates from the ciliated cells. After separation into a gel and a sol phase, lysozyme and lactoferrin are enriched in the salivary gel phase suggesting that mucus may act as a matrix for 'protective' proteins on the mucosal surface. A salivary MUC5B N-terminal fragment consistent with a cleavage event in the D' domain was detected with antibodies against various N-terminal peptide sequences suggesting that assembly of MUC5B occurs through a mechanism similar to that of the von Willebrand factor. Identification of additional cleavage sites C-terminal to the D' domain suggests that most of the N-terminal low-glycosylated part of MUC5B may be removed without affecting the oligomeric nature of the mucin. Possibly, the generation of mucins with different macromolecular properties through proteolytic 'processing' is one way of adapting the mucus polymer matrix to meet local physiological demands. Monomeric mucins that appear to turn over rapidly in the airway epithelium have been identified using radiolabelled mucin precursors. 'Shedding' of such mucins after microbe attachment may prevent colonization of epithelial surfaces.

Animals↗