Activation of factor XII in acetone-treated human plasma: significance of the functional state of plasma kallikrein for the extent of activation.
The kaolin-induced activation of factor XII (XII) to XIIa was studied in plasminogen-free human citrated plasma treated with acetone in the presence of benzamidine 7.5 mM. XIIa was assayed as prekallikrein (PK) activator. The significance of the concentrations of XII, PK and high molecular weight kininogen (HMrK) was examined using mixtures of normal plasma and plasma genetically deficient in these factors. At the high plasma dilution used (1 + 23 v/v in the kaolin incubate) a joint estimation of the factors was obtained. A reduction in amount of XII, PK or HMrK resulted in a correspondingly reduced yield of XIIa. Plasma kallikrein present was assayed as S-2302 amidase. The concentration of PK in XII-deficient plasma was normal, in HMrK-deficient plasma about 30% of normal. The activation of XII was studied in fresh plasma as well as in plasma stored for 3-6 months at -70 degrees, and the activation with acetone was carried out in the presence and in the absence of benzamidine, EDTA or purified HMrK. In previous work benzamidine was found to protect the cofactor function of purified HMrK in the assay system used, and EDTA was found to inhibit purified human plasma kallikrein assayed as plasminogen activator. The present results support the previous observations, and indicate that acetone treatment of fresh human plasma (benzamidine present) results in the activation of plasma kallikrein in a functional state that requires kinin-free, but otherwise native HMrK as a cofactor for the activation of XII.(ABSTRACT TRUNCATED AT 250 WORDS)
D000096:Acetone / Q000633:toxicity*; D000328:Adult; D001550:Benzamidines / Q000494:pharmacology; D005174:Factor XII / Q000378:metabolism*; D015956:Factor XIIa; D006801:Humans; D007610:Kallikreins / Q000502:physiology*; D008297:Male; D008970:Molecular Weight; D010446:Peptide Fragments / Q000378:metabolism; D010958:Plasminogen / Q000494:pharmacology
D001550:Benzamidines; D010446:Peptide Fragments; D000096:Acetone; D005174:Factor XII; D010958:Plasminogen; D007610:Kallikreins; D015956:Factor XIIa; C032157:benzamidine