Enhanced UDP-Galactose: Glycoprotein Galactosyl Transferase Activity in Cultivated Skin Fibroblasts from Patients with Cystic Fibrosis and Its Possible Relationship to the Pathogenesis of the Disease

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Abstract
Summary: Homogenates of cultivated skin fibroblasts derived from patients with cystic fibrosis had a higher level of UDP-galactose:ovalbumin galactosyl transferase activity compared to fibroblasts derived from control subjects. The activity in control subjects was 1.82 ± 0.43 nmol galactose transferred/hr/mg protein, whereas the activity in fibroblasts of patients was 2.95 ± 0.77. The difference was significant at P < 0.01. Activity in the fibroblasts of obligate heterozygotes was 2.15 ± 0.60. The difference between the activities in fibroblasts of heterozygotes and patients was significant at P < 0.05. The activity in control fibroblasts could be enhanced by basic polypeptides like polylysine, polyarginine, histone, and protamine but not by neutral or acidic polypeptides. Fibroblasts from patients released significantly higher amounts of a soluble form of the enzyme activity into the culture medium than control fibroblasts. Speculation: The enhanced UDP-galactose:ovalbumin galactosyl transferase observed in fibroblasts of patients with cystic fibrosis may explain many of the abnormalities observed in cystic fibrosis, namely, enhanced glycoprotein secretion, elevated levels of calcium in mucous secretions and obstruction of ducts. The mechanism of enhanced activity is unknown; however, if the primary defect lies in defective α2-macroglobulin-protease complexes, the resulting deficient proteolytic activity could generate the “factors” previously identified in the disease. These “factors” may interact with UDP-galactose:glycoprotein galactosyl transferase in a manner similar to that observed with the model polypeptides employed in this study, enhancing its activity.