SUBSTRATES OF HAGEMAN FACTOR : I. Isolation and Characterization of Human Factor XI (PTA) and Inhibition of the Activated Enzyme by α1-Antitrypsin

Unactivated partial thromboplastin antecedent (PTA) has been purified by sequential chromatography of plasma on quaternary aminoethyl Sephadex, sulphoprophyl Sephadex, Sephadex G-150, and passage over an anti-IgG immunoadsorbant. The preparation gave a single band after alkaline disc gel electrophoresis, sodium dodecyl sulfate (SDS) gel electrophoresis and isoelectric focusing in acrylamide gels and was found to have a mol wt of 175,000 by gel filtration, 163,000 by SDS gel electrophoresis, and an isoelectric point of 8.8–9.4 (peak 9.0–9.1). Pre-PTA was activated directly by activated Hageman factor or by Hageman factor prealbumin fragments. Its coagulant activity was inhibited by DFP, soybean trypsin inhibitor and trasylol but not by lima bean trypsin inhibitor or ovomucoid trypsin inhibitor indicating that activated PTA possesses the same inhibition profile utilizing these reagents as does plasma kallikrein. A major plasma inhibitor of activated PTA was found to be a 65,000 mol wt α-globulin which was isolated free of α1-chymotrypsin inhibitor, inter α-trypsin inhibitor, α2-macroglobulin, and the other known inhibitors of activated PTA, the activated first component of complement (C1 INH), and antithrombin III. Its physicochemical properties were identical to α1-antitrypsin, and it was absent in α1-antitrypsin-deficient plasma thereby identifying this PTA inhibitor as α1-antitrypsin.

[1]  P. Lee,et al.  Preparation, Characterization, and Activation of a Highly Purified Factor XI: Evidence that a Hitherto Unrecognized Plasma Activity Participates in the Interaction of Factors XI and XII , 1974, British journal of haematology.

[2]  A. Kaplan,et al.  Fletcher factor deficiency. A diminished rate of Hageman factor activation caused by absence of prekallikrein with abnormalities of coagulation, fibrinolysis, chemotactic activity, and kinin generation. , 1974, The Journal of clinical investigation.

[3]  R. Rosenberg,et al.  Anticoagulant Action of Heparin , 1973, Nature.

[4]  K. Wuepper PREKALLIKREIN DEFICIENCY IN MAN , 1973, The Journal of experimental medicine.

[5]  K. Wuepper,et al.  ACTIVATION OF HAGEMAN FACTOR IN SOLID AND FLUID PHASES , 1973, The Journal of experimental medicine.

[6]  O. Ratnoff,et al.  Partial purification of plasma thromboplastin antecedent (factor XI) and its activation by trypsin. , 1973, The Journal of clinical investigation.

[7]  I. Liener,et al.  The purification of human serum 1 -antitrypsin by affinity chromatography on concanavalin A. , 1973, Biochemical and biophysical research communications.

[8]  K. Austen,et al.  THE FIBRINOLYTIC PATHWAY OF HUMAN PLASMA , 1972, Journal of Experimental Medicine.

[9]  O. Ratnoff,et al.  The inhibitory properties of plasma against activated plasma thromboplastin antecedent (factor XIa) in hereditary angioneurotic edema. , 1972, The Journal of laboratory and clinical medicine.

[10]  O. Ratnoff,et al.  Partial purification and some properties of a plasma inhibitor of activated plasma thromboplastin antecedent (factor XI). , 1972, The Journal of laboratory and clinical medicine.

[11]  O. Ratnoff Studies on the product of the reaction between activated Hageman factor (factor XII) and plasma thromboplastin antecedent (factor XI). , 1972, The Journal of laboratory and clinical medicine.

[12]  D. McConnell Inhibitors of kallikrein in human plasma. , 1972, The Journal of clinical investigation.

[13]  K. Austen,et al.  A PREALBUMIN ACTIVATOR OF PREKALLIKREIN III. APPEARANCE OF CHEMOTACTIC ACTIVITY FOR HUMAN NEUTROPHILS BY THE CONVERSION OF HUMAN PREKALLIKREIN TO KALLIKREIN , 1972 .

[14]  P. Harpel Separation of plasma thromboplastin antecedent from kallikrein by the plasma 2 -macroglobulin, kallikrein inhibitor. , 1971, The Journal of clinical investigation.

[15]  K. Austen,et al.  A PREALBUMIN ACTIVATOR OF PREKALLIKREIN , 1971, The Journal of experimental medicine.

[16]  D. Deutsch,et al.  Plasminogen: Purification from Human Plasma by Affinity Chromatography , 1970, Science.

[17]  C. Forbes,et al.  Inhibition of activated Hageman factor and activated plasma thromboplastin antecedent by purified serum C1 inactivator. , 1970, The Journal of laboratory and clinical medicine.

[18]  Kaplan Ap,et al.  A pre-albumin activator of prekallikrein. , 1970, Journal of immunology.

[19]  K. Weber,et al.  The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. , 1969, The Journal of biological chemistry.

[20]  B. C. Hummel,et al.  Quantitative enzymic assay of human plasminogen and plasmin with azocasein as substrate , 1965 .

[21]  J. Niemetz,et al.  A NORMAL INHIBITOR OF THE BLOOD COAGULATION CONTACT REACTION PRODUCT. , 1965, Blood.

[22]  O. Ratnoff,et al.  Studies on the action of Hageman factor: evidence that activated Hageman factor in turn activates plasma thromboplastin antecedent. , 1961, The Journal of clinical investigation.