Anaphylatoxin inactivator of human plasma: its isolation and characterization as a carboxypeptidase

TLDR

Human serum lacks anaphylatoxin activity because it contains a potent inactivator. The inactivator was purified as an alpha‑globulin of approximately 310 kDa. The enzyme inactivates C3‑ and C5‑derived anaphylatoxins and bradykinin, releases C‑terminal arginine, hydrolyzes hippuryl‑L‑arginine and hippuryl‑L‑lysine, is inhibited by EDTA or phenanthroline, and resembles a metal‑dependent pancreatic carboxypeptidase B.

Abstract

The failure of human serum to give rise to anaphylatoxin activity could be attributed to the presence of a potent inactivator of anaphylatoxin in human serum. The inactivator was isolated and characterized as an alpha-globulin with a molecular weight of approximately 310,000. It was found to abolish the activity of both anaphylatoxins, which are derived respectively from the third and the fifth component of complement, and of bradykinin. Inactivation of C3-derived anaphylatoxin and of bradykinin was accompanied by release of C-terminal arginine from these peptides. The anaphylatoxin inactivator was shown to hydrolyze the synthetic substrates hippuryl-L-arginine and hippuryl-L-lysine and to be inhibited by ethylenediaminetetraacetate (EDTA) or phenanthroline. These observations indicate that the anaphylatoxin inactivator constitutes a metal-dependent enzyme resembling in specificity pancreatic carboxypeptidase B.