RESPIRATORY MUCINS - IDENTIFICATION OF CORE PROTEINS AND GLYCOFORMS

At least eight mucin apoproteins are expressed by the tracheobronchial epithelium, but it is not known which, if any, of these are major con stituents of the respiratory secretions responsible for the formation of the mucus gel. To address this we have isolated mucins from normal, asthmatic and chronic bronchitic secretions, The asthmatic mucin redu ced subunits were fractionated into four populations (I-IV) by anion-e xchange HPLC. Amino acid and monosaccharide compositional analysis, as well as M(r) and size measurements, indicate that two of these popula tions (I and II) are glycoforms of the same or related apoprotein(s) a nd that the other populations contain two different apoproteins. A pan el of antibodies and antisera recognizing the variable number tandem r epeat (VNTR) of specific mucin apoproteins did nor, as predicted, reac t with the glycosylated molecules, but after deglycosylation the major ity of these probes (with the exception of those to MUC2, which were n egative) reacted at a low level with each of the subunit populations. In contrast, an antiserum against a non-VNTR sequence of MUC5AC identi fied one of the populations (III) as the MUC5AC mucin. The MUC5AC redu ced subunit had an M(r) of 2.2 x 10(6) and an R(G) (radius of gyration ) of 57 nm. The genetic identities of the major mucin (populations I a nd II) and a minor component (population IV) were not established. The MUC5AC mucin was also identified as a major component in the pooled n ormal secretions from 20 individuals, whereas in a chronic bronchitic sample it was only a minor constituent. Furthermore, in all these diff erent respiratory secretions the MUC5AC mucin appears as a similar bio chemical entity, as assessed by Mono Q chromatography and agarose elec trophoresis, suggesting that it may have a well-defined pattern of gly cosylation in the respiratory tract.