Observations on the in vitro Effects of Chylomicra, Low-Density Lipoproteins and Phospholipids on Human Plasma Euglobulin Lysis

Summary

Data have been presented on the in vitro effects of human chylomicra, low-density human plasma lipoproteins, and partially purified preparations of various phospholipids on human plasma euglobulin lysis. Euglobulin lysis was found to be accelerated by preparations of mixed soybean phospholipids (aso-lectin), cephalin, phosphatidyl inositol, phophatidyl serine and phosphatidyl ethanolamine. In contrast, it was found to be inhibited by preparations of human chylomicra, low-density human plasma liproproteins and lecithin. Inhibition of euglobulin lysis produced by any of these three agents could be diminished or completely overcome by the simultaneous presence of suitable levels of any one of the accelerating agents. In all cases studied, both inhibitory and accelerating effects were observed to be concentration-dependent. Evidence has been obtained to suggest that in the case of the accelerating agents the observed increased rate of euglobulin lysis is not a direct effect on lysis itself, but rather is due to more complete precipitation of plasminogen in the presence of these substances. On the other hand, it appears that the inhibitory effects observed are not related to the extent of plasminogen precipitation, but are actually true inhibitions of euglobulin lysis. The possible clinical significance of some of these observations has been briefly discussed.

^* This investigation was supported by the Medical Research and Development Board, Office of the Surgeon General, Department of the Army, under Contract No. DA-49-193-MD-2171 and by The National Heart Institute, National Institutes of Health, under Grant No. H-3940.

• References

• 1 Greig H. B. W. Inhibition of Fibrinolysis by Alÿnentary Lipaemia. Lancet II: 16 1956;
• 2 Scott R. F, Thomas W. A. Methods for Comparing Effect of Various Fats on Fibrinolysis. Proc. Soc. exp. Biol. (N. Y) 96: 24 1957;
• 3 Buckell M, Elliott FrankA. Effect of Butter Lipemia on the Rate of Clot Lysis in Normal Males. 662. 1959
• 4 Bang N. U, Cliffton E. E. The Effect of Alimentary Hyperlipemia on Thrombolysis in vivo. Thrombos. Diathes. haemorrh. 04: 149 1960;
• 5 Scott R. F, Alousi K, Thomas W. A. Dietary Lipids, Thrombosis and Clot Lysis. Arch. Path. 71: 595 1961;
• 6 Cliffton E. E, Burchell A. R. Inhibition of Fibrinolysis by Hyperlipemia. Thrombos. Diathes. haemorrh. 06: 463 1961;
• 7 Merigan T. C, Farquhar J. W, Williams J. H, Sokolow M. Effect of Chylomicrons on the Fibrinolytic Activity of Normal Human Plasma in Vitro. Circulât. Res. 07: 205 1959;
• 8 Farquhar J. W, Merigan T. C, Sokolow M. Plasma Fibrinolysis in Man: The Effect of Chylomicrons Derived from Different Dietary Fats. J. exp. Med. 113: 587 1961;
• 9 Sarkar N. Reduced Fibrinolytic Activity of Atherosclerotic Sera Caused by an Increase in Low-Density Lipoproteins in Blood. Nature 189: 929 1961;
• 10 Barnard R. D, Barnard J. F. Fibrinolysis and Lipemia. Lancet 271: 516 1956;
• 11 Greig H. B. W, Cornelius E. M. Fat Emulsions and Fibrinolysis. Brit. J. exp. Path. 42: 568 1961;
• 12 Folch J. Brain Cephalin, a Mixture of Phosphatides-Separation from it of Phosphatidyl Serine, Phosphatidyl Ethanolamine, and a Fraction Containing an Inositol Phosphatide. J. biol. Chem. 146: 35 1942;
• 13 Folch J. The Chemical Structure of Phosphatidyl Serine. J. biol. Chem. 174: 439 1948;
• 14 Remmert L. F, Cohen P. P. Partial Purification and Properties of a Proteolytic Enzyme of Human Serum. J. biol. Chem. 181: 431 1949;
• 15 Gerbeck C, Koppel J. L, Olwin J. H. Effects of Certain Phospholipids on Plasminogen Activation and Plasmin Activity. Thrombos. Diathes. haemorrh. 07: 16 1962;
• 16 Astrup T, Mullertz S. The Fibrin Plate Method for Estimating Fibrinolytic Activity. Arch. Biochem. 40: 346 1952;
• 17 Lowry O. H, Rosebrough N. J, Farr A. L, Randall R. J. Protein Measurement with the Folin Phenol Reagent. J. biol. Chem. 193: 265 1951;
• 18 Beveridge J. M. R, Johnson S. E. The Determination of Phospholipid Phosphorus. Canad. J. Res. 27: 159 1949;
• 19 Von Kaulla K. N, McDonald T. S. The Effect of Heparin on Components of the Human Fibrinolytic System. Blood 13: 811 1958;
• 20 Johnson S. A, Schneider C. C. The Existence of Antifibrinolysin Activity in Platelets. Science 117: 229 1953;
• 21 Stefanini M, Murphy I. S. Human Platelets as Source of Antifibrinolysin. J. clin. Invest 35: 355 1956;
• 22 Hume R. An Inhibitory Effects of Platelets on Fibrinolysis. Scot. Med. J. 03: 479 1958;
• 23 Steichele D. F, Herschlein H. J. Proaktivator und Antiplasmingehalt der Thrombozyten des Menschen und verschiedene Versuchstiere. Med. Welt. 1961 1855..
• 24 Lewis J. H, Wilsan J. H, Merchant W. R. A Streptokinase Cofactor in Human Platelets. Proc. Soc. exp. Biol. (N. Y) 109: 248 1962;
• 25 Iatridis S. G, Ferguson J. H. Effect of Surface and Hageman Factor on the Endogenous or Spontaneous Activation of the Fibrinolytic System. Thrombos. Diathes. haemorrh. 06: 411 1961;
• 26 Iatridis S. G, Ferguson J. H. Active Hageman Factor: A Plasma Lysokinase of the Human Fibrinolytic System. J. clin. Invest 41: 1277 1962;