Abstract

  Background and Objectives

 The most important component of fibrinolytic system is the proenzyme plasminogen that through various activators is converted to its active form plasmin and performs its vital functions that is fibrin clot lysis. The first anti human plasminogen antibody was prepared by Ploplis in 1982 and its effect was studied. Since then many researchers have attempted to prepare and study anti plasminogen antibodies to elucidate important aspects of structure and activation mechanism of plasminogen , physiologic condition of fibrinolysis, etc. In the present study, we studied the probable effects of three antihuman plasminogen monoclonal antibodies A₄D₁₀, A₅E₁₀ and A₂C₈ on the activation of the fibrinolytic system.

  Materials and Methods

  After separate steps like the culture of antibody-producing hybridoma cells, their injection to mice, extraction of the ascites fluid and purification of antibodies were taken, various methods such as optical evaluation of plasma clot lysis in the presence of antibodies, quantitative measurement of DD/E in D-dimer assay, evaluation with ELIZA assay using S-2251 synthetic substrate lysis and the like were used to study the effects of thses antibodies.

  Results

  Primary observations with human pooled plasma showed that in the presence of plasminogen activators (t-PA, u-PA and SK), A₅E₁₀ and A₄D₁₀ can enhance activation of fibrinolytic system, but A₃B₂ has no effect on this system. According to D- dimer assay, it was shown that the lytic effects of A₅E₁₀ and A₄D₁₀ antibodies were dose dependent the higher the amount of antibodies, the lower their effects. The other test performed with S-2251 synthetic substrate showed plasminogen activation in the presence of Urokinase therefore, lysis of this substrate enhanced in the presence of A₅E₁₀ and A₄D₁₀ antibodies. Moreover, in this test ineffectiveness of A3B2 on plasminogen activation was confirmed .

  Conclusions

  In conclusion, we suggested A₄D₁₀ and A₅E₁₀ antibodies by modification of structural from of plasminogen facilitate its activation in presence of plasminogen activators.

  Key words : Fibrinolytic, Plasminogen, Monoclonal antibody, Plasminogen activators