Abstract
The complement system is an important immune mechanism mediating both recognition and elimination of foreign bodies. The lectin pathway is one pathway of three by which the complement system is activated. The characteristic protease of this pathway is Mannan-binding lectin (MBL)-associated serine protease 2 (MASP2), which cleaves complement proteins C2 and C4. We present a novel and alternative role of MASP2 in the innate immune system. We have shown that MASP2 is capable of promoting fibrinogen turnover by cleavage of prothrombin, generating thrombin. By using a truncated active form of MASP2 as well as full-length MASP2 in complex with MBL, we have shown that the thrombin generated is active and can cleave both factor XIII and fibrinogen, forming cross-linked fibrin. To explore the biological significance of these findings we showed that fibrin was covalently bound on a bacterial surface to which MBL/MASP2 complexes were bound. These findings suggest that, as has been proposed for invertebrates, limited clotting may contribute to the innate immune response.
Highlights
The immune system is composed of many recognition and effector mechanisms the primary role of which is to eliminate invading pathogens, altered host cells and macromolecules
In fig 1B we show SDS-PAGE analysis of the fragmentation of prothrombin when incubated with factor Xa or truncated rMASP2 construct (trMASP2)
This was confirmed by N-terminal sequencing of the prethrombin 2 fragment formed by trMASP2
Summary
The immune system is composed of many recognition and effector mechanisms the primary role of which is to eliminate invading pathogens, altered host cells and macromolecules. The complement system is one such system, and it is composed mainly of plasma proteins of which several circulate as serine protease zymogens. These, when activated, catalyse downstream events of the complement system resulting in an inflammatory response, direct lysis and opsonization of microorganisms. The other two activation pathways are initiated by spontaneous hydrolysis of C3 (alternative pathway) or upon binding of mannan-binding lectin (MBL) or ficolins to sugars or N-acetylated groups on the surface of microorganisms (lectin pathway) [2]. Neither MBL nor ficolins possess enzyme activity themselves but rely on the MBL-associated serine proteases (MASPs) and 3, with which they circulate in complexes [3]. When MBL, L-ficolin or H-ficolin bind to a bacterial surface, the MASPs, which are homologues of C1r and C1s, become activated. Of the three MASPs only MASP2 is capable of activating complement by cleavage of C4 and C2. [4]
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