Trypsin binding activity of alpha 2-macroglobulin in cystic fibrosis and other lung diseases.

Abstract

Abnormalities of the interaction between alpha 2-macroglobulin and proteases have been suspected in cystic fibrosis. We measured the binding activity for trypsin of alpha 2-macroglobulin in 65 patients with cystic fibrosis, 41 obligate heterozygotes for cystic fibrosis, 18 children with asthma, 21 adult patients with chronic obstructive pulmonary disease, and 21 healthy control subjects. The assay was based on the observation that, once it is bound to alpha 2-macroglobulin, trypsin is no longer inhibited by soybean trypsin inhibitor. The bound trypsin retains activity against synthetic substrates such as N-alpha-benzoyl-arginine-p-nitroanilide. We found a moderately increased molar binding ratio of trypsin to alpha 2-macroglobulin in all patient groups and heterozygotes compared to healthy control subjects. The absolute concentration of alpha 1-macroglobulin was related to age rather than to the disease of the patient. Our data argue against a defect in protease-binding activity of alpha 2-macroglobulin in cystic fibrosis. The moderately increased binding activity observed could have been related to a structural difference in alpha 2-macroglobulin or to binding of ligands. This finding however, was not unique to patients with cystic fibrosis; the binding activity was increased in heterozygotes and in patients with other pulmonary diseases.