Identification of prekallikrein and high-molecular-weight kininogen as a complex in human plasma.

Abstract

Prekallikrein and high-molecular-weight kininogen were associated in normal human plasma at a MW of 285,000, as assessed by gel filtration on Sephadex G-200. The MW of prekallikrein in plasma that is deficient in high-molecular-weight kininogen was 115,000. This prekallikrein could be isolated at a MW of 285,000 after plasma deficient in high-molecular weight kininogen was combined with plasma that is congenitally deficient in prekallikrein. Addition of purified 125I-labeled prekallikrein and high-molecular-weight kininogen to the respective deficient plasma yielded a shift in the molecular weight of prekallikrein, and complex formation could be demonstrated by incubating prekallikrein with high-molecular weight kininogen. Prekallikrein and high-molecular-weight kininogen are physically associated in plasma as a noncovalently linked complex and may therefore be adsorbed together during surface activation of Hageman factor. The complex is disrupted when these proteins are isolated by ion exchange chromatography.