پتانسيل آنتي پلاسمينوژن منوكلونال آنتي بادي در دستكاري دو سيستم فيبرينوليز و آنژيوژنز

The potential of antiplasminogen monoclonal antibodies in fibrinolytic & angiogenesis system manipulation

, , , l Background: Plasminogen has a central role in fibrinolyrtic system can activate through various activators (PAs) to its active form plasmin and perfoem its vital function that is fibrin clot lysis. Furthermore the fibrinolyrtic system plays a major role in angiogenesis. The fibrinolyrtic system activation control cell migration and invasion. In addition to this, plasmin regulates tumor growth. Monoclonal antibodies, as biological tools, play an important role in basic researches. Methods: In the first step the effects of antibodies on the activation of fibrinolyrtic system with PAs were evaluated with several methods including macroscopic observation, quantitative measurement of DD/E fragments by D-dimer assay and activation of plasminogen by S-2251 synthetic substrate (ELISA method), subsequently we studied the effect of antibodies on angiogenesis process in an in- vitro model. Results: Results showed that MC2B8 that is an inhibitor of plasminogen activation in presence of plasminogen activators can inhibit angiogenesis process: A1D12 that is against N-terminal domain of Glu-plasminogen, in addition to activation of fibrinolyrtic system in presence of plasminogen activators, can activate in vitro angiogenesis process. Conclusion: Plasmin formation is a critical step in invasion and migration of endothelial cells to form new vessels. Plasmin directly participates in angiogenesis by direct fibrin and other matrix components degradation, and indirectly by activating matrix degrading metalloproteinase and angiogenic growth factors. According to the in- vitro results, MC2B8 and A1D12 monoclonal antibodies play roles in this process in a dose dependent manner.