Abnormal breakdown of alpha2-macroglobulin-trypsin complex in cystic fibrosis

The complex of trypsin with purified alpha2-macroglobulin from normals and patients with cystic fibrosis was studied. The formed complex failed to reveal any proteolytic activity toward a high molecular weight substrate whereas the esterolytic activity towards a low molecular weight substrate was retained. This esterolytic activity was resistant to inhibition by a high molecular weight inhibitor. During iincubation at 38 degrees C the complex with normal alpha2-macroglobulin was slowly inhibited by the high molecular weight inhibitor and regained activity with the high molecular weight substrate. This phenomenon was not obtained when the alpha2-macroglobulin from cystic fibrosis was examined. These data suggest that the gradual conversion of normal alpha2-macroglobulin-trypsin complex into an alpha2-macroglobulin fragment-trypsin complex is deficient in patients with cystic fibrosis.