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Updated: May 14, 2026

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
Published on: January 7, 2019
The role of MASP-1/3 in complement activation
Hideharu Sekine1, Minoru Takahashi, Daisuke Iwaki
1Department of Immunology, Fukushima Medical University School of Medicine, 1-Hikariga-oka, Fukushima 960-1295, Japan.
Insights
Mannose-binding lectin-associated serine proteases (MASPs) MASP-1 and MASP-3 are crucial for activating the complement system's alternative pathway. These proteases also appear to play a role in the lectin pathway's activation.
Area of Science:
- Immunology
- Complement System Biology
Background:
- The complement system comprises over 30 proteins, activating via classical, lectin, or alternative pathways for pathogen destruction.
- Mannose-binding lectin (MBL) and ficolins initiate the lectin pathway, activating MBL-associated serine proteases (MASPs).
- MASP-2 is essential for C3 convertase assembly, but the roles of MASP-1 and MASP-3 are largely unknown.
Purpose of the Study:
- To elucidate the physiological functions of MASP-1 and MASP-3 within the complement system.
- To investigate the involvement of MASP-1 and MASP-3 in the lectin and alternative pathways.
Main Methods:
- Generation of a MASP-1 and MASP-3 deficient (M1/3 KO) mouse model.
- In vitro enzymatic assays to assess the activity of MASP-1 and MASP-3 on Factor D and other MASPs.
Main Results:
- M1/3 KO mice exhibited a complete lack of alternative pathway activation due to inactive Factor D.
- MASP-1 and MASP-3 demonstrated the ability to activate Factor D proenzyme in vitro.
- MASP-1 was shown to activate MASP-2 and MASP-3, analogous to C1r's activation of C1s.
Conclusions:
- MASP-1 and MASP-3 are essential for the activation of the alternative complement pathway.
- These proteases are implicated in the activation mechanisms of both the lectin and alternative pathways.
Abstract:
The complement system, which consists of more than 30 plasma and cell surface proteins, is activated by three pathways: the classical, lectin, and alternative pathways, leading to the generation of opsonins and pathogen destruction. In the lectin pathway, mannose-binding lectin (MBL) and ficolins act as pattern recognition molecules for pathogens, resulting in the activation of MBL-associated serine proteases (MASPs: MASP-1, MASP-2, and MASP-3). Among these proteases, MASP-2 is a key enzyme that cleaves C4 and C2 to assemble a C3 convertase (C4b2a). However, the physiological function of MASP-1 and MASP-3 remains unclear. To investigate the roles of MASP-1 and MASP-3, we generated a MASP-1- and MASP-3-deficient (M1/3 KO) mouse model and found that the deficient mice lacked alternative pathway activation because factor D (Df) remained as a proenzyme in the serum. MASP-1 and MASP-3 were able to convert the proenzyme of Df to an active form in vitro. In addition, MASP-1 was able to activate MASP-2 and MASP-3 as C1r activates C1s. Thus, MASP-1 and MASP-3 seem to be involved in activation of both the lectin and alternative pathways.
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