SIALOMUCIN COMPLEX IN THE RAT RESPIRATORY-TRACT - A MODEL FOR ITS ROLE IN EPITHELIAL PROTECTION

The pulmonary epithelium has a multitude of specialized functions, whi ch depend on regulated growth and differentiation of several cell type s. One such function is the synthesis and secretion of mucins, which o ffer the epithelium protection from and a means for removal of noxious environmental factors. Sialomucin complex (SMC) is a heterodimeric gl ycoprotein consisting of a mucin subunit (ASGP-1, ascites sialoglycopr otein-1) and a transmembrane protein (ASGP-2) with two epidermal-growt h-factor-like domains. SMC was originally discovered in a highly metas tatic rat mammary adenocarcinoma and has been implicated in metastasis and in the protection of the tumour cells from natural killer cells. It can also act as a ligand for the receptor tyrosine kinase 185(neu), suggesting that it is bifunctional as well as heterodimeric. SMC is e xpressed on the epithelium of rat conducting airways, with the highest levels occurring in the proximal trachea and progressively decreasing into the bronchioles. Airway SMC consists of two forms: a soluble for m that lacks the C-terminal cytoplasmic and transmembrane domains and accounts for about 70% of the total, and a membrane-associated form th at has the C-terminal domains, Immunocytochemical analyses show that S MC is predominantly present on the apical surfaces of the airway epith elium, but not in goblet cells. Soluble form can be removed from the t rachea by rinsing, suggesting that a fraction of the protein is adsorb ed to the apical surface. Based on these results, we propose a protect ive mechanism in which membrane and soluble forms of SMC are produced by airway luminal epithelial cells to provide a cell-associated epithe lial glycoprotein barrier that also serves as an interface with flowin g mucus. In support of this mechanism, we demonstrated secretion of so luble SMC by primary cultures of tracheal epithelial cells. This model suggests that SMC is a critical element in the protective barrier of the airway epithelium.