Revised mechanism of complement lectin-pathway activation revealing the role of serine protease MASP-1 as the exclusive activator of MASP-2.
The lectin pathway of complement activation is an important component of the innate immune defense. The initiation complexes of the lectin pathway consist of a recognition molecule and associated serine proteases. Until now the autoactivating mannose-binding lectin-associated serine protease (MASP)-2 has been considered the autonomous initiator of the proteolytic cascade. The role of the much more abundant MASP-1 protease was controversial. Using unique, monospecific inhibitors against MASP-1 and MASP-2, we corrected the mechanism of lectin-pathway activation. In normal human serum, MASP-2 activation strictly depends on MASP-1. MASP-1 activates MASP-2 and, moreover, inhibition of MASP-1 prevents autoactivation of MASP-2. Furthermore we demonstrated that MASP-1 produces 60% of C2a responsible for C3 convertase formation.
Department of Biochemistry, Eötvös Loránd University, H-1117 Budapest, Hungary.
Dávid
D
Héja
Andrea
A
Kocsis
József
J
Dobó
Katalin
K
Szilágyi
Róbert
R
Szász
Péter
P
Závodszky
Gábor
G
Pál
Péter
P
Gál
D001777:Blood Coagulation; D003167:Complement Activation; D050577:Complement C3-C5 Convertases / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D037102:Lectins; D050577:Complement C3-C5 Convertases; C084067:MASP1 protein, human; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases