INTERACTIONS OF ACTIVATED HAGEMAN FACTOR (Factor Xlla, HFa) WITH NORMAL Cl-INHIBITOR

Abstract

Purified Hageman factor activated with a mixture of brain sulfatides and bovine serum albumin (BSA) developed clot-promoting activity which was inhibited by purified normal human Cl-inhibitor, but during extended incubation there was an apparent loss of inhibition in these mixtures. When a preparation of Hageman factor fragments (HFf), which had a much lower specific Hageman factor coagulant activity, was incubated with BSA-sulfatides, its_coagulant activity was also enhanced and could be inhibited by normal Cl-inhibitor. When the HFa having a molecular weight of approximately 75,000 was mixed with the HFf preparation before Cl-inhibitor was added, there was a progressive shortening of the Hageman factor specific clotting times with increasing amounts of HFf in the mixtures, despite the addition of Cl-inhibitor. Moreover, as the amounts of HFf in the mixtures were increase a high molecular weight complex of about 190,000 containing HFa and Cl-inhibitor could no longer be identified in SDS-gel electrophoresis but a low molecular weight band (127,000) appeared, which probably contained HFf of about 22,000 molecular weight and Cl-inhibitor. Therefore, HFf appeared to compete effectively with the HFa (75,000) for Cl-inhibitor in these mixtures of purified reagents. It is also possible that HFf may have interacted with the HFa or the Cl-inhibitor changing the steric configuration of either one so that an interaction between HFa and Cl-inhibitor did not occur.