Abstract
Previous studies in our laboratory have demonstrated the absence of an α2M-protease complex in activatad plasma of patients with CF (Padlat. Res. 10:812, 1976). Recently we have documented decreasad complex formation of CF α2M with various andoproteases as compared to normal α2M; CF heterozygotes gave intermediate values (Biochem. Biophys. Res. Commun. 71:864, 1976). This study was undertaken in ordar to furthar characterize the differences in the α2M from CF patients as compared to normal controls. The kinetic properties of purified α2M from 3 healthy donors were compared to those of α2M from 3 patients with CF. The binding affinity of α2M to bovine trypsin was determined from its inhibition of benzoyl-arginine ethyl ester hydrolysis by trypsin. A typical competitive inhibition was obtained with a Ki value of 6 × 10−7 M for normal α2M and of 3 × 10−6 M for CF α2M. The Km value for α2M-trypsin complex for this substrate was 5 × 10−4 M for normal α2M-trypsin complex and 4 × 10−5 M for the CF α2M complex. Upon incubation at 38° C, the normal α2M-trypsin complex gradually regained partial activity towards high molecular weight substrate and susceptibility to soybean trypsin inhibitor inhibition. In contrast, this phenomenon could not be demonstrated with the CF α2M-trypsin complexes.
These studies provide additional evidence that the α2M in CF is functionally abnormal and provide an explanation for tha presence of the various CF factors of a polypeptide nature.
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Shapira, E., Martin, C. & Nadlar, H. FUNCTIONALLY ABNORMAL α2-MACROGLOBULIN (α2M) IN CYSTIC FIBROSIS (CF). Pediatr Res 11, 464 (1977). https://doi.org/10.1203/00006450-197704000-00564
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DOI: https://doi.org/10.1203/00006450-197704000-00564
