Mechanism of Human Plasminogen Activation by Streptokinase and Human Plasmin^[*]

Summary

A sensitive tool has been described for measuring fibrinolysis in reconstituted systems using thrombelastography. Activator mixtures with no appreciable proteolytic activity can similarly be tested in this system when the fibrinogen utilized has sufficient plasminogen present. Exposure of human plasminstreptokinase mixtures formed at pH 7.0 to acid conditions produced a striking loss of activator activity which could not be ascribed to low pH lability of the components, nor to plasmin action on the SK at pH 2.0. This is additional evidence for the hypothesis that human plasmin interacts with SK to form a complex capable of converting human and bovine plasminogen to plasmin.

^* Obtained through the courtesy of the American National Red Cross from E. R. Squibb and Sons.

^** Now at the US Army Research Institute of Environmental Medicine, Natick, Massachusetts.

^*** Deceased.

• References

• 1 Astrup T. Fibrinolysis in the organism. Blood 11: 781 1956;
• 2 Müllertz S. Activation of plasminogen. Ann. N. Y. Acad. Sci. 68: 38 1957;
• 3 Siegel M, Cliffton E. E. Mechanism of in vitro activation of human fibrinolytic system: Differential titration of the components. J. appl. Physiol. 10: 289 1957;
• 4 Alkjaersig N, Fletcher A. P, Sherry S. The activation of human plasminogen. II. A kinetic study of activation with trypsin, urokinase, and streptokinase. J. biol. Chem. 233: 86 1958;
• 5 Kline D. L, Fishman J. B. Plasmin: the humoral protease. Ann. N. Y. Acad. Sci. 68: 25 1957;
• 6 Ablondi F. B, Hagan J. J. Comparison of certain properties of human plasminogen and “proactivator”. Proc. Soc. exp. Biol. (N. Y) 95: 195 1957;
• 7 Hayashi T, Maekawa S. Studies on the activating factors in fibrinolytic system. II. Streptococcal and staphylococcal fibrinolysis. Jap. J. exp. Med. 24: 287 1954;
• 8 Zylber J, Blatt W. F, Jensen H. Mechanism of bovine plasminogen activation by human plasmin and streptokinase. Proc. Soc. exp. Biol. (N. Y) 102: 755 1959;
• 9 Hartert H. Die Thrombelastographie. Eine Methode zur physikalischen Analyse des Blutgerinnungsvorganges. Z. ges. exp. Med. 117: 189 1951;
• 10 Blombäck B, Blombäck M. Purification of bovine and human fibrinogen. Acta chem. scand. 10: 147 1956;
• 11 Sale E. E, Priest S. G, Jensen H. Studies on the antiproteolytic activity of bovine blood. J. biol. Chem. 227: 83 1957;
• 12 Meyers W. M, Burdon K. L. Proteolytic activity of guinea pig serum activated by streptokinase human plasminogen preparations. Amer. J. Physiol. 190: 303 1957;