The Inter-α-Trypsin Inhibitor as Precursor of the Acid-Stable Proteinase Inhibitors in Human Serum and Urine

Abstract

A small amount of antitryptic activity is detectable in the supernatant of deproteinized human serum. Preincubation of serum with trypsin causes an increase in acid-stable antitryptic activity. This rise in activity depends on the inter-.alpha.-trypsin inhibitor concentration. The native inhibitor present in normal sera, and in higher concentrations in sera of patients with nephropathies, and the trypsin-liberated inhibitor show immunological cross reaction with antibodies to the serum inter-.alpha.-trypsin inhibitor. The 2 inhibitors differ in MW and electrophoretic mobility. The physiological inhibitor (I-34), with a MW of 34,000 and a high carbohydrate content, can be transformed by trypsin into an inhibitor (I-17) with a MW of 17,000. This inhibitor is identical with the inhibitors liberated by trypsin from serum or from purified inter-.alpha.-trypsin inhibitor. The acid-stable inhibitor from urine is identical with the physiological serum inhibitor. Analogously, this inhibitor is transformed by trypsin into the inhibitor with a MW of 17,000. The inter-.alpha.-trypsin inhibitor is probably the precursor of both the physiological and the trypsin-liberated inhibitor. By a mechanism as yet unknown, but most likely a limited proteolysis, the secreted inhibitor is liberated from the high MW precursor. In contrast to the monospecific trypsin-inhibiting precursor, the physiological and artificially liberated inhibitors are trypsin/chymotrypsin/plasmin inhibitors.