Abstract
Extract: A protein with an isoelectric point (pI) of 5.48 was found to be deficient in plasma from most cystic fibrosis (CF) homozygotes and obligate heterozygote carriers for CF as compared with normal control plasma. Purification of the protein with a pI of 5.48 from normal plasma was performed using ammonium sulfate precipitation, DEAE-cellulose and CM-cellulose chromatography, Sephadex G-200 gel filtration, starch block clectrophoresis, and Sepharose 4B gel filtration. The purified protein migrated as a single band on polyacrylamide gel electrophoresis, and displayed a single arc on immunoelectrophoresis against polyvalent antiserum to whole human serum. Results from various techniques used in its characterization indicate that this protein is a fragment of α2-macroglobulin (α2M) which is derived from α2M by proteolytic cleavage of intact α2M subunits. Quantitation of α2M levels in plasma indicated no significant differences between levels of α2M in CF homozygote, obligate heterozygote carrier, or normal control plasma samples. Quantitation of arginine esterase activity in plasma treated with chloroform and ellagic acid indicated that both the total arginine esterase activity and that fraction of arginine esterase activity inhibited by soybean trypsin inhibitor (SBTI) were decreased in most CF homozygote and obligate heterozygote plasma samples relative to normal control values. The results of this study indicate that plasma samples from CF homozygotes and obligate heterozygote carriers for CF show deficient proteolytic cleavage of α2M as compared with normal control plasma, and suggest that a structural abnormality in α2M or a deficiency in plasma proteolytic activity may be responsible for this deficiency in proteolysis.
Speculation: An abnormality in the binding affinity of α2M for plasma proteases may account for the presence of “factors” in CF homozygotes and obligate heterozygote carriers.
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Wilson, G., Fudenberg, H. Studies on Cystic Fibrosis Using Isoelectric Focusing. II. Demonstration of Deficient Proteolytic Cleavage of α2-Macroglobulin in Cystic Fibrosis Plasma. Pediatr Res 10, 87–96 (1976). https://doi.org/10.1203/00006450-197602000-00003
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DOI: https://doi.org/10.1203/00006450-197602000-00003
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