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Revised mechanism of complement lectin-pathway activation revealing the role of serine protease MASP-1 as the exclusive activator of MASP-2

Héja, Dávid, Kocsis, Andrea, Dobó, József, Szilágyi, Katalin, Szász, Róbert, Závodszky, Péter, Pál, Gábor, Gál, Péter
Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.26 pp. 10498-10503
blood serum, complement, humans, immune response, lectins, proteolysis, serine proteinases
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.