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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

Author:
Héja, Dávid, Kocsis, Andrea, Dobó, József, Szilágyi, Katalin, Szász, Róbert, Závodszky, Péter, Pál, Gábor, Gál, Péter
Source:
Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.26 pp. 10498-10503
ISSN:
0027-8424
Subject:
blood serum, complement, humans, immune response, lectins, proteolysis, serine proteinases
Abstract:
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.
Agid:
1721430