Effects of Certain Phospholipids on Plasminogen Activation and Plasmin Activity^[*]

Summary

Crude and partially purified phospholipid preparations have been studied for their effects on a) the activation of purified human plasminogen by streptokinase and b) the activity of plasmin resulting from such activation. Plasmin activity has been measured as BAMe esterase, caseinolytic, and fibrinolytic activities.

Plasmin BAMe esterase activity was significantly enhanced by phosphatidyl inositol and phosphatidyl serine but only slightly by phosphatidyl ethanolamine. Preparations of asolectin and cephalin, although not having any effect on plasmin BAMe esterase activity per se, did appear to increase plasminogen activation by streptokinase. None of the above-mentioned effects was observed when plasmin caseinolytic activity was measured. The phospholipid preparation having the greatest effect on plasmin BAMe esterase activity, phosphatidyl inositol, also exhibited an effect on plasmin fibrinolytic activity. With both BAMe esterase and fibrinolytic activities the effects produced by the phospholipid materials were concentration dependent and, in the case of fibrinolytic activity, increased concentrations beyond the optimum level resulted in a gradual diminution in activity and eventual inhibition.

• References

• 1 O’Brien J. R. Fat Ingestion. Blood Coagulation, and Atherosclerosis. Amer. J. med. Sci 1958; 234: 373
• 2 Koppel J. L, Olwin J. H. Fat Intake and Metabolism: Their Relation to Blood Coagulation and Atherosclerosis. Ill. Med. J 1961; 119: 304
• 3 Greig H. B. W. Inhibition of Fibrinolysis by Alimentary Lipaemia. Lancet 1956; 2: 3
• 4 Greig H. B. W, Runde I. A. Studies on the Inhibition of Fibrinolysis by Lipids. Lancet 1957; 2: 461
• 5 Greig H. B. W. The Effect of Lipid Extraction on the Fibrinolytic Activity of Plasma. S. Afr. J. med. Sci 1957; 22: 37
• 6 Scott R. F, Thomas W. A. Methods for Comparing Effect of Various Fats on Fibrinolysis. Proc. Soc. exp. Biol. (N. Y.) 1957; 96: 24
• 7 Buckell M, Elliot F. A. Effect of Butter Lipaemia on the Rate of Clot Lysis in Normal Males. Lancet 1959; 1: 662
• 8 Scott R. F, Alousi K, Thomas W. A. Dietary Lipids. Thrombosis, and Clot-Lysis. Arch. Path. (Chicago) 1961; 71: 595
• 9 Merigan T. C, Farquhar J. W, Williams J. H, Sokolow M. Effect of Chylomicrons on the Fibrinolytic Activity of Normal Human Plasma in Vitro. Circulat. Res 1959; 7: 205
• 10 Farquhar J. W, Merigan T. C, Sokolow M. Plasma Fibrinolysis in Man: The Effect of Chylomicrons Derived from Different Dietary Fats. J. exp. Med 1961; 113: 587
• 11 Kwaan H. C, MacFadzean A. J. S. Plasma Fibrinolysis In Vivo by Feeding Cholesterol. Nature 1957; 179: 260
• 12 Michell J. R. A, Briers S. M. Effect of Cholesterol. Cholesterol Esters, and Neutral Fats on Fibrinolysis. Lancet 1959; 2: 435
• 13 Gillman T, Naidoo S. S, Hathorn M. Sex Differences in Plasma Fibrin. Fibrinolytic Capacity, and Lipids as Influenced by Ingested Fat, Gonadectomy, and Hormone Inplants. Clin. Sci 1958; 17: 393
• 14 Bang N. U, Cliffton E. E. The Effect of Alimentary Hyperlipemia on Thrombolysis in vivo. Thromb. Diath. haem 1960; 4: 149
• 15 Cliffton E. E, Burchell A. R. Inhibition of Fibrinolysis by Hyperlipemia. Thromb. Diath. haem 1961; 5: 463
• 16 Hougie C, Ayers F. Lipaemia and Fibrinolytic Potentiality. Lancet 1960; 1: 186
• 17 Bronte-Stewart B. Lipids and Atherosclerosis. Fed. Proc 1961; 20: 127
• 18 Johnson S. A, Schneider C. C. The Existence of Antifibrinolysin Activity in Platelets. Science 1953; 117: 229
• 19 Stefanini M, Murphy I. S. Human platelets as a Source of Antifibrinolysin. J. clin. Invest 1956; 35: 355
• 20 Hume R. An Inhibitory Effect of Platelets on Fibrinolysis. Scot. med. J 1958; 3: 479
• 21 Kline D. L. The Purification and Crystallization of Plasminogen (Profibrinolysin). J. biol. Chem 1953; 204: 949
• 22 Alkjaersig N, Fletcher A. P, Sherry S. The Activation of Human Plasminogen. J. biol. Chem 1958; 233: 86
• 23 Folch J. Brain Cephalin, a Mixture of Phosphatides-Separation from it of Phosphatidyl Serine, Phosphatidil Ethanolamine, and a Fraction Containing an Inositol Phosphatide. J. biol. Chem 1942; 146: 35
• 24 Remmert L. F, Cohen P. P. Partial Purification and Properties of a Proteolytic Enzyme of Human Serum. J. biol. Chem 1949; 181: 431
• 25 Ratnoff O. D, Menzie C. A New Method for the Determination of Fibrinogen in Small Samples of Plasma. J. Lab. clin. Med 1951; 37: 316
• 26 Astrup T, Müllertz S. The Fibrin Plate Method for Estimating Fibrinolytic Activity. Arch. Biochem 1952; 40: 346
• 27 Folch J. The Chemical Structure of Phosphatidyl Serine. J. biol. Chem 1948; 174: 439
• 28 Markus G, Ambrus C. M. On the Formation of Different Types of Plasmin by Streptokinase Activation. J. biol. Chem 1960; 235: 1673
• 29 Authors Unpublished Observations.
• 30 Miale J. B, Garrett V. R. Studies on the Thromboplastin Generation Test. III. The Effects of Dilution, Storage and Concentration of Platelets. Amer. J. clin. Path 1957; 27: 701
• 31 Connor W. E, Carter J. R. Influence of Soybean Phosphatide on Blood Coagulation and its Use in the Thromboplastin Generation Test. Proc. Soc. exp. Biol. (N. Y.) 1958; 97: 38
• 32 Gobbi F, Stefanini M. The Coagulation Defect of Plasma Poor in Platelets and Phospholipids. Its Correction by Tissue Phospholipids. Acta haemat. (Basel) 1959; 21: 272
• 33 Wallach D. E, Maurice P. A, Steele B. B, Surgenor D. M. Studies on the Relationship between the Colloidal State and Clot-promoting Activity of Pure Phosphatidyl Ethanolamines. J. biol. Chem 1959; 234: 2829