STRUCTURAL FEATURES OF THE CORE PROTEINS OF HUMAN AIRWAY MUCINS ASCERTAINED BY CDNA CLONING

Tracheobronchial secretions are one of the most important elements of the mucociliary system that protects the respiratory mucosa. They contain bronchial mucus, which is composed of a group of macromolecules secreted by the goblet cells of the epithelium and the submucosal glands. Bronchial mucins are the most characteristic molecules of this mucus. They form a group of complex, polydispersed O-linked glycoproteins containing sugars, which make up 80% of their weight. The protein core of human airway mucin has been difficult to sequence by traditional technologies because of its high content of serine and threonine residues linked to numerous oligosaccharide chains. We therefore prepared a lambda-gt11 cDNA library from one sample of human tracheobronchial mucosa and screened this library with a polyclonal antibody directed against the apopeptides of human bronchial mucins. We obtained 20 positive clones that were sequenced. These sequences were classified into three different types. The use of the nucleotide probes from these clones in Northern blot analysis showed that the RNA messages were extremely polydispersed. At the current time, four of these probes allow us to map human tracheobronchial mucins genes to at least three different chromosomes. These results suggest that the peptide moiety of the human airway mucin is very heterogeneous.