Cystic fibrosis. I. Fractionation of the mucociliary inhibitor from plasma

A protein fraction present in low concentrations in plasma of cystic fibrosis homozygotes and heterozygotes has been identified by its biologic activity in ciliary preparations of gills from Crassos trea virginica, where it causes mucociliary inhibition. In the present study, mucociliary inhibition was shown to be associated with an IgG-rich fraction. The cystic fibrosis mucociliary inhibitor was obtained as a low molecular weight protein after dissociation from IgG in 5 M guanidinium chloride. Gel filtration of the dissociated ultrafiltrate fraction on Bio-Gel P-30 isolated the cystic fibrosis mucociliary inhibitor activity in a pool containing protein of 6,000 to 12,000 MW. The mucociliary inhibitor was heterogeneous upon isoelectric focusing, with inhibition demonstrated in a focused range of pH 4.6 to 6.1 and in a fraction focused near pH 9. Lectin- affinity chromatography of the low molecular weight proteins dissociated from the IgG fraction of a cystic fibrosis homozygote demonstrated that at least one molecular species of the mucociliary inhibitor contained a carbohydrate moiety, since inhibitory fractions were found both in the nonadsorbed fraction and in the fraction eluted with N-acetylglucosamine.Copyright Speculation: Protein fractions present in low concentrations in plasma of cystic fibrosis genotypes that cause mucociliary inhibition in ciliary preparations of gills from Crassotrea virginica have been characterized and appear to be structurally related to the urinary cystic fibrosis mucociliary inhibitor which has been purified. These molecules may be helpful in studies to test the feasibility of developing immunologic assays for prenatal diagnosis and heterozygote detection.