ABSTRACT
The structural crosslinking of mucus depends on several molecular factors (Fig. 1). These include intramolecular disulfide bonds that hold the mucin subunits together, entanglement crosslinks that occur because of the very high molecular weight, and various types of noncovalent bonds due to the partially charged oligosaccharide side chains characteristic of mucins (1,2). We have seen that agents that alter the ionic interactions or the hydrogen bonding of the mucous gel can produce potentially beneficial effects on mucus rheology and clearability. This was found to be the case with hypertonic saline (3-5) and with dextran (6,7), a compound that can also block bacterial adhesion (8) to epithelial cells.As part of our ongoing search for improvements in mucoactive treatments, we have looked at mucoactive agents that might alter both the hydrogen bonds and the ionic interactions. We found that one such agent-charged, low molecular weight (LMW) heparin-had a greater mucolytic and mucokinetic capacity than the neutral saccharide polymer dextran. This was seen both in in vitro rheo-* Current affiliation: Hospital of Printing Bureau of Ministry of Finance, Tokyo, Japan, t Current affiliation: Brigham & Women’s Hospital, Harvard Medical School, Boston, Massachusetts.
