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 |
