Abstract
As demonstrated by others, fibrinolytic activity was generated in diluted, acidified normal plasma exposed to kaolin, a process requiring Hageman factor (Factor XII). Generation was impaired by adsorbing plasma with glass or similar agents under conditions which did not deplete its content of Hageman factor or plasminogen. The defect could be repaired by addition of a noneuglobulin fraction of plasma or an agent or agents eluted from diatomaceous earth which had been exposed to normal plasma. The restorative agent, tentatively called Hageman factor-cofactor, was partially purified by chromatography and had an apparent molecular weight of approximately 165,000. It could be distinguished from plasma thromboplastin antecedent (Factor XI) and plasma kallikrein, other substrates of Hageman factor, and from the streptokinase-activated pro-activator of plasminogen. Evidence is presented that an additional component may be needed for the generation of fibrinolytic activity in mixtures containing Hageman factor, HF-cofactor, and plasminogen.
The long-recognized generation of plasmin activity in chloroform-treated euglobulin fractions of plasma was found to be dependent upon the presence of Hageman factor. Whether chloroform activation of plasminogen requires Hageman factor-cofactor was not determined, but glass-adsorbed plasma, containing Hageman factor and plasminogen, did not generate appreciable fibrinolytic or caseinolytic activity.
These studies emphasize the complex nature of the mechanisms which lead to the generation of plasmin in human plasma.
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Selected References
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- ALKJAERSIG N., FLETCHER A. P., SHERRY S. The activation of human plasminogen. I. Spontaneous activation in glycerol. J Biol Chem. 1958 Jul;233(1):81–85. [PubMed] [Google Scholar]
- ALKJAERSIG N., FLETCHER A. P., SHERRY S. The mechanism of clot dissolution by plasmin. J Clin Invest. 1959 Jul;38(7):1086–1095. doi: 10.1172/JCI103885. [DOI] [PMC free article] [PubMed] [Google Scholar]
- AZNAR J., LOPEZ-BORRASCA A. HAGEMAN FACTOR IN THE FIBRINOLYTIC SYSTEM. Lancet. 1965 Feb 20;1(7382):437–438. doi: 10.1016/s0140-6736(65)90046-2. [DOI] [PubMed] [Google Scholar]
- AZNAR J. PROPIEDADES FIBRINOLITICAS DEL "FACTOR CONTACTO". Rev Esp Fisiol. 1964 Jun;20:43–51. [PubMed] [Google Scholar]
- BIDWELL E. Fibrinolysins of human plasma; a comparison of fibrinolytic plasma from normal subjects and from cadaver blood with plasmin prepared by activation with chloroform. Biochem J. 1953 Oct;55(3):497–506. doi: 10.1042/bj0550497. [DOI] [PMC free article] [PubMed] [Google Scholar]
- CLARKE R. L., ORANDI A., CLIFFTON E. E. Induction of fibrinolysis by venous obstruction. Angiology. 1960 Oct;11:367–370. doi: 10.1177/000331976001100501. [DOI] [PubMed] [Google Scholar]
- Colman R. W., Mattler L., Sherry S. Studies on the prekallikrein (kallikreinogen)--kallikrein enzyme system of human plasma. I. Isolation and purification of plasma kallikreins. J Clin Invest. 1969 Jan;48(1):11–22. doi: 10.1172/JCI105959. [DOI] [PMC free article] [PubMed] [Google Scholar]
- EISEN V. EFFECT OF HEXADIMETHRINE BROMIDE ON PLASMA KININ FORMATION, HYDROLYSIS OF P-TOSYL-L-ARGININE METHYL ESTER AND FIBRINOLYSIS. Br J Pharmacol Chemother. 1964 Feb;22:87–103. doi: 10.1111/j.1476-5381.1964.tb01546.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eisen V. Kinin formation and fibrinolysis in human plasma. J Physiol. 1963 May;166(3):514–529. doi: 10.1113/jphysiol.1963.sp007120. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forman W. B., Ratnoff O. D., Boyer M. H. An inherited qualitative abnormality in plasma fibrinogen: fibrinogen Cleveland. J Lab Clin Med. 1968 Sep;72(3):455–472. [PubMed] [Google Scholar]
- HOLEMANS R., ROBERTS H. R. HAGEMAN FACTOR AND IN VIVO ACTIVATION OF FIBRINOLYSIS. J Lab Clin Med. 1964 Nov;64:778–786. [PubMed] [Google Scholar]
- IATRIDIS S. G., FERGUSON J. H. Actie Hageman factor: a plasma lysokinase of the human fibrinolytic system. J Clin Invest. 1962 Jun;41:1277–1287. doi: 10.1172/JCI104590. [DOI] [PMC free article] [PubMed] [Google Scholar]
- IATRIDIS S. G., FERGUSON J. H. Effect of physical exercise on blood clotting and fibrinolysis. J Appl Physiol. 1963 Mar;18:337–344. doi: 10.1152/jappl.1963.18.2.337. [DOI] [PubMed] [Google Scholar]
- Iatridis P. G., Ferguson J. H. Plasminoplastin generation test of normal, HF-, PTA-, X-, PTC-, and AHF- platelet-poor plasmas: evidence that only HF- plasma has an abnormal fibrinolytic activity. Nature. 1965 Sep 25;207(5004):1404–1405. doi: 10.1038/2071404a0. [DOI] [PubMed] [Google Scholar]
- Iatridis S. G., Iatridis P. G., Ferguson J. H. The role of HF (factor XII) in the pathogenesis of the thrombolytic state induced by venous occlusion. Thromb Diath Haemorrh. 1966 Jul 31;16(1):207–217. [PubMed] [Google Scholar]
- KLINE D. L., FISHMAN J. B. Proactivator function of human plasmin as shown by lysine esterase assay. J Biol Chem. 1961 Oct;236:2807–2812. [PubMed] [Google Scholar]
- Kass L., Ratnoff O. D., Leon M. A. Studies on the purification of antihemophilic factor (factor 8. I. Precipitation of antihemophilic factor by concanavalin A. J Clin Invest. 1969 Feb;48(2):351–358. doi: 10.1172/JCI105991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kellermeyer R. W., Ratnoff O. D. Abolition of the permeability-enhancing properties of Hageman factor by specific antiserum. J Lab Clin Med. 1967 Sep;70(3):365–371. [PubMed] [Google Scholar]
- LEWIS J. H., FERGUSON J. H. Studies on a proteolytic enzyme system of the blood. Activation of profibrinolysin by serum fibrinolysokinase. Proc Soc Exp Biol Med. 1951 Oct;78(1):184–188. doi: 10.3181/00379727-78-19014. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- MACKAY M., MAYCOCK W. D., COMBRIDGE B. S. Activation of endogenous plasma proteolytic enzymes with the consequent production of pharmacologically active polypeptides. Nature. 1962 Sep 22;195:1206–1207. doi: 10.1038/1951206a0. [DOI] [PubMed] [Google Scholar]
- MARKUS G., AMBRUS C. M. Selective inactivation of the plasminogen contaminant in thrombin. Nature. 1960 Nov 12;188:582–583. doi: 10.1038/188582a0. [DOI] [PubMed] [Google Scholar]
- MULLERTZ S. A plasminogen activator in spontaneously active human blood. Proc Soc Exp Biol Med. 1953 Feb;82(2):291–295. doi: 10.3181/00379727-82-20097. [DOI] [PubMed] [Google Scholar]
- MULLERTZ S. Formation and properties of the activator of plasminogen and of human and bovine plasmin. Biochem J. 1955 Nov;61(3):424–434. doi: 10.1042/bj0610424. [DOI] [PMC free article] [PubMed] [Google Scholar]
- NIEWIAROWSKI S., PROU-WARTELLE O. [Role of the contact factor (Hageman factor) in fibrinolysis]. Thromb Diath Haemorrh. 1959 Sep 1;3:593–603. [PubMed] [Google Scholar]
- OGSTON D., FULLERTON H. W. Changes in fibrinolytic activity produced by physical activity. Lancet. 1961 Sep 30;2(7205):730–733. doi: 10.1016/s0140-6736(61)90685-7. [DOI] [PubMed] [Google Scholar]
- RATNOFF O. D., COLOPY J. E. A familial hemorrhagic trait associated with a deficiency of a clot-promoting fraction of plasma. J Clin Invest. 1955 Apr;34(4):602–613. doi: 10.1172/JCI103109. [DOI] [PMC free article] [PubMed] [Google Scholar]
- RATNOFF O. D., COLOPY J. E., PRITCHARD J. A. The blood-clotting mechanism during normal parturition. J Lab Clin Med. 1954 Sep;44(3):408–415. [PubMed] [Google Scholar]
- RATNOFF O. D., CRUM J. D. ACTIVATION OF HAGEMAN FACTOR BY SOLUTIONS OF ELLAGIC ACID. J Lab Clin Med. 1964 Mar;63:359–377. [PubMed] [Google Scholar]
- RATNOFF O. D., DAVIE E. W., MALLETT D. L. Studies on the action of Hageman factor: evidence that activated Hageman factor in turn activates plasma thromboplastin antecedent. J Clin Invest. 1961 May;40:803–819. doi: 10.1172/JCI104314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- RATNOFF O. D., DAVIE E. W. The purification of activated Hageman factor (activated factor XII). Biochemistry. 1962 Nov;1:967–975. doi: 10.1021/bi00912a005. [DOI] [PubMed] [Google Scholar]
- RATNOFF O. D., MILES A. A. THE INDUCTION OF PERMEABILITY-INCREASING ACTIVITY IN HUMAN PLASMA BY ACTIVATED HAGEMAN FACTOR. Br J Exp Pathol. 1964 Jun;45:328–345. [PMC free article] [PubMed] [Google Scholar]
- REMMERT L. F., COHEN P. P. Partial purification and properties of a proteolytic enzyme of human serum. J Biol Chem. 1949 Nov;181(1):431–448. [PubMed] [Google Scholar]
- Ratnoff O. D. Activation of Hageman factor by L-homocystine. Science. 1968 Nov 29;162(3857):1007–1009. doi: 10.1126/science.162.3857.1007-a. [DOI] [PubMed] [Google Scholar]
- Ratnoff O. D., Pensky J., Ogston D., Naff G. B. The inhibition of plasmin, plasma kallikrein, plasma permeability factor, and the C'1r subcomponent of the first component of complement by serum C'1 esterase inhibitor. J Exp Med. 1969 Feb 1;129(2):315–331. doi: 10.1084/jem.129.2.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SAWYER W. D., FLETCHER A. P., ALKJAERSIN N., SHERRY S. Studies on the thrombolytic activity of human plasma. J Clin Invest. 1960 Feb;39:426–434. doi: 10.1172/JCI104054. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SCHOENMAKERS J. G., KURSTJENS R. M., HAANEN C., ZILLIKEN F. PURIFICATION OF ACTIVATED BOVINE HAGEMAN FACTOR. Thromb Diath Haemorrh. 1963 Jul 31;35:546–556. [PubMed] [Google Scholar]
- SIEGELMAN A. M., CARLSON A. S., ROBERTSON T. Investigation of serum trypsin and related substances. I. The quantitative demonstration of trypsinlike activity in human blood serum by a micromethod. Arch Biochem Biophys. 1962 Apr;97:159–163. doi: 10.1016/0003-9861(62)90058-9. [DOI] [PubMed] [Google Scholar]
- Smink M. M., Daniel T. M., Ratnoff O. D., Stavitsky A. B. Immunologic demonstration of a deficiency of Hageman factor-like material in Hageman trait. J Lab Clin Med. 1967 May;69(5):819–832. [PubMed] [Google Scholar]
- TODD A. S. The histological localisation of fibrinolysin activator. J Pathol Bacteriol. 1959 Jul;78:281–283. doi: 10.1002/path.1700780131. [DOI] [PubMed] [Google Scholar]
- WEINER M., REDISCH W., STEELE J. M. Occurrence of fibrinolytic activity following administration of incotinic acid. Proc Soc Exp Biol Med. 1958 Aug-Sep;98(4):755–757. doi: 10.3181/00379727-98-24174. [DOI] [PubMed] [Google Scholar]