Partial purification of a serum inhibitor of C'1-esterase.

The first component of human complement (C’l) has been reported to exist in serum as a proenzyme which can be activated by antigen-antibody aggregates (l-5), plasmin (1, B), and, in a partially purified state, by autocatalysis (6, 7) to an enzyme, C’l-e&erase, capable of hydrolyzing certain synthetic amino acid esters, notably N-acetyl-L-tyrosine ethyl ester (6-8), and interacting with the fourth and second components of human complement (C’4 and C’2) (3, 7). Both conversion of proenzyme to enzyme and enzymatic activity were inhibited by a substance of fresh human serum which was nondialyzable, heatlabile (56”, 30 minutes), and unrelated to any of the recognized components of human complement (6, 8). Subsequent studies (9) indicated that in human serum, C’l-esterase inhibitor was labile at 0” at pH values below 5.5 or in the presence of low concentrations of methanol, but could be recovered quantitatively in the supernatant fraction of serum containing 40% saturated ammonium sulfate. A modification of the chromatographic method of Boman (10, 11) for the separation of serum proteins has yielded substantially purified C’l-esterase inhibitor containing only traces of trypsin and plasmin inhibitors. This method has also been utilized by Moll, Sunden, and Brown (12) for the al-globulin trypsin inhibitor in serum of pregnant women and by Bundy and Mehl (13) for purification of crl-globulin trypsin inhibitor in normal human plasma. The present paper describes a partial purification procedure for C’l-esterase inhibitor and some properties of the purified inhibitor. Its behavior in various immune systems will be reported separately. The data to be presented demonstrate that serum inhibitor of C’l-esterase is distinct from serum trypsin or plasmin inhibitors. A preliminary report of this work has appeared in abstract form (14).