Studies on a nocal sevine protease and the activation mechanism of the lectin complement pathway

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Mannose-binding lectin (MBL) and L-ficolin/P35 are human serum lections that are complexed with MASP. Upon binding of these complexes to carbohydrates on the surfaces of microbes, MASP cleaves C2,C3 and C4 resulting in activation of the complement system (lectin pathway). Three types of MASP (MASP-1, -2 and -3) have been identified so far. sMAP, a splicing variant of MASP-2, is also associated with MBL and L-ficolin/P35. MBL forms mainly three types of oligomer with different sizes. The Composition of MASPs in the complex varies from oligomer to oligomer. In this research project we obtained the following main results.1. We succeeded in the separation of L-ficolin/P35 and MASPs/sMAP from the complex. L-ficolin/P35 binds to MASPs and sMAP with similar dissociation constants to those for the interaction between MBL and MASPs/sMAP.2. We developed a method for the separation ofMASP-1 and MASP-3.3. Hakata antigen activates the lectin pathway in association with MASPs and sMAP.4. MASP-1 has a ability to cleave the factor IX of the clotting system, while MASP-2 and MASP-3 have low and no activities, respectively.5. T98G cells, a cell line of human glioma, produce Hakata antigen, MASP-1 and MASP-3.