α2-Macroglobulin-proteinase complexes in cystic fibrosis serum Analysis by monoclonal antibodies and receptor-mediated endocytosis by normal human fibroblasts

Abstract

α 2-Macroglobulin complexed to proteinases activated during clotting of cystic fibrosis and control sera was quantitated with the complex-specific monoclonal antibody F 2B 2. Similar amounts of α 2-macroglobulin complexes (between 40 and 90 μg/ml) were generated in cystic fibrosis and control sera. Endocystosis of the complexes by normal fibroblasts was compared to the amount of complexes detected by the F 2B 2-radioimmunoassay. Normal uptake was observed with 13 out of 14 cystic fibrosis sera. One cystic fibrosis serum showed strongly reduced endocytosis of the complexes. Complexes isolated from this serum on immobilized F 2B 2 failed to inhibit binding of purified α 2-macroglobulin-trypsin to its receptor, demonstrating deficient receptor-binding of these complexes. The low complexes could not be distinguised from complexes isolated from control or other cystic fibrosis sera by isoelectric focusing, rate electrophoresis or SDS-polyacrylamide gel electrophoresis.