Simultaneous activation of complement and coagulation by MBL-associated serine protease 2.
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.
Krarup
Anders
A
MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, Oxford, United Kingdom. anders.krarup@bioch.ox.ac.uk
Wallis
Russell
R
Presanis
Julia S
JS
Gál
Péter
P
Sim
Robert B
RB
D000818:Animals; D001777:Blood Coagulation / Q000235:genetics / Q000502:physiology*; D003167:Complement Activation / Q000502:physiology*; D006224:Cricetinae; D005176:Factor XIII / Q000378:metabolism; D015951:Factor Xa / Q000235:genetics / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D037601:Mannose-Binding Lectin / Q000378:metabolism*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011516:Prothrombin / Q000235:genetics / Q000378:metabolism
D037601:Mannose-Binding Lectin; D010446:Peptide Fragments; D011516:Prothrombin; D005337:Fibrin; D005340:Fibrinogen; D005176:Factor XIII; C012007:prethrombins; D050606:Mannose-Binding Protein-Associated Serine Proteases; D015951:Factor Xa