In the airway, hyaluronan is not only found in the submucosal, connective tissue compartment, but also on the luminal, ciliated surface of the airway epithelium, as shown by histochemistry of human and ovine tracheal sections using a biotinylated hyaluronan-binding protein. The role of hyaluronan in the airway is likely multifold. Hyaluronan forms a continuous three-dimensional chain network with the ability to absorb and release water, thereby contributing to the hydration and thus, rheological properties of mucus, critical for proper mucociliary function. However, hyaluronan plays other roles in the connective tissue, providing a concentration-dependent osmotic pressure and regulating macromolecular movement by acting as a size-exclusion "gel." Such hyaluronan functions can also be expected in the airways. While hyaluronan is made by airway submucosal gland cells, it is possible that cells of the superficial epithelium, including ciliated cells, contribute to its production. The finding of apically and luminally "secreted" hyaluronan is not unique to the airway. Polarized release of hyaluronan by epithelial cells at the apical surface has been described in retinal, endometrial, and mammary epithelial cells. Removal of hyaluronan from the airway lumen is complex, as at least part of luminal hyaluronan seems protected from mucociliary clearance. Initial breakdown of hyaluronan is required for its removal and this is likely accomplished by ROS.
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