RELATIONSHIP OF CONTACT ACTIVATION COFACTOR (CAC) PROCOAGULANT ACTIVITY TO KININOGEN

  • 1 January 1977
    • journal article
    • research article
    • Vol. 49  (6) , 935-945
Abstract
Contact activation cofactor (CAC) facilitates the interaction of factors XI and XII. Patients lacking CAC have a coagulation defect and are deficient in high MW kininogen. The coincidence of these 2 defects suggests that a single protein may be responsible for both physiologic functions. Immunologic and activity studies were made on isolated CAC to clarify the relationship between CAC and kininogen. CAC forms a single precipitin line with anti-human kininogen, and antikininogen neutralizes CAC activity. CAC and high MW kininogen show a reaction of identity on immunodiffusion against rabbit anti-CAC. Anti-CAC forms 2 precipitin lines with normal plasma which can be identified as high and low MW kininogen. Monospecific immunoabsorbed anti-CAC forms a single precipitin line with plasma high MW kininogen and neutralizes CAC activity. Cleavage of kinin fragment from CAC by insoluble trypsin or kallikrein does not proportionally reduce procoagulant activity. CAC neutralized by anti-ACA can release kinins on exposure to trypsin or kallikrein. The results support the conclusions that CAC procoagulant activity is a function of high MW kininogen, that antigenic determinants unique to high MW kininogen are shared by the CAC portion of the molecule, and that the clotting reactions may occur at a site removed from the kinin peptide.