The Human Plasma Kinin System II. Contact Activation of Plasma Prekallikrein and Factor XI in Factor XII-Deficient Plasma 1

Summary

Noncontacted factor XII-deficient human plasma was mixed with Celite, the protein adsorbed to the Celite was eluted with a concentrated salt solution, and then chromatographed on QAE-Sephadex A-50, followed by Sephadex G-200.

The first (excluded) peak obtained by anion exchange chromatography contained substances with physicochemical and biological properties indistinguishable from plasma kallikrein and “contact activation product.” Material obtained with the excluded peak enhanced vascular permeability, hydrolyzed arginine ester, liberated kinin from both fresh and heated plasma, corrected the prolonged clotting time of plasmas congenitally deficient in factors XII or XI, artificially depleted of XI, but did not enhance the clotting of plasmas deficient in factors IX, VIII, and X. On gel filtration the molecular weight of kallikrein was estimated to be about 90, 000 and that of the clot-promoting material was about 170,000. The latter was confirmed by sucrose density gradient ultracentrifugation.

We conclude that prekallikrein and factor XI can be activated directly by massive exposure to an active surface. This activation does not seem to require factor XII. It is further concluded that the clot-promoting activity of contact activation product is due to factor XI. Finally, we could obtain no prekallikrein-activating material from factor XII-deficient plasma.