| First Author | Takahashi M | Year | 2010 |
| Journal | J Exp Med | Volume | 207 |
| Issue | 1 | Pages | 29-37 |
| PubMed ID | 20038603 | Mgi Jnum | J:156544 |
| Mgi Id | MGI:4420855 | Doi | 10.1084/jem.20090633 |
| Citation | Takahashi M, et al. (2010) Essential role of mannose-binding lectin-associated serine protease-1 in activation of the complement factor D. J Exp Med 207(1):29-37, S1-3 |
| abstractText | The complement system is an essential component of innate immunity, participating in the pathogenesis of inflammatory diseases and in host defense. In the lectin complement pathway, mannose-binding lectin (MBL) and ficolins act as recognition molecules, and MBL-associated serine protease (MASP) is a key enzyme; MASP-2 is responsible for the lectin pathway activation. The function of other serine proteases (MASP-1 and MASP-3) is still obscure. In this study, we generated a MASP-1- and MASP-3-deficient mouse model (Masp1/3-/-) and found that no activation of the alternative pathway was observed in Masp1/3-/- serum. Mass spectrometric analysis revealed that circulating complement factor D (Df) in Masp1/3-/- mice is a zymogen (pro-Df) with the activation peptide QPRGR at its N terminus. These results suggested that Masp1/3-/- mice failed to convert pro-Df to its active form, whereas it was generally accepted that the activation peptide of pro-Df is removed during its secretion and factor D constitutively exists in an active form in the circulation. Furthermore, recombinant MASP-1 converted pro-Df to the active form in vitro, although the activation mechanism of pro-Df by MASP-1 is still unclear. Thus, it is clear that MASP-1 is an essential protease of both the lectin and alternative complement pathways. |
