Mannose-binding lectin (MBL)-associated serine protease (MASP)-1 contributes to activation of the lectin complement pathway.
The complement system plays an important role in innate immunity. In the lectin complement pathway, mannose-binding lectin (MBL) and ficolins act as recognition molecules, and MBL-associated serine protease (MASP) is a key enzyme. It has been suggested that MASP-2 is responsible for the activation of C4. Other serine proteases (MASP-1 and MASP-3) are also associated with MBL or ficolins; however, their functions are still controversial. In this study, a MASP-1- and MASP-3-deficient mouse model (MASP1/3(-/-)) was generated by a gene targeting strategy to investigate the roles of MASP-1 and MASP-3 in the lectin pathway. Serum derived from MASP1/3(-/-) mice showed significantly lower activity of both C4 and C3 deposition on mannan-agarose, and this low activity was restored by the addition of recombinant MASP-1. MASP-1/3-deficient serum showed a significant delay for activation of MASP-2 compared with normal serum. Reconstitution of recombinant MASP-1 in MASP-1/3-deficient serum was able to promote the activation of MASP-2. From these results, we propose that MASP-1 contributes to the activation of the lectin pathway, probably through the activation of MASP-2.
Takahashi
Minoru
M
Department of Immunology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, Japan.
Iwaki
Daisuke
D
Kanno
Kazuko
K
Ishida
Yumi
Y
Xiong
Jie
J
Matsushita
Misao
M
Endo
Yuichi
Y
Miura
Shigeto
S
Ishii
Naoto
N
Sugamura
Kazuo
K
Fujita
Teizo
T
D000818:Animals; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism*; D003181:Complement C4 / Q000235:genetics / Q000378:metabolism*; D037582:Complement Pathway, Mannose-Binding Lectin / Q000502:physiology*; D037102:Lectins / Q000235:genetics / Q000378:metabolism; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000378:metabolism*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000097604:Ficolins
D003176:Complement C3; D003181:Complement C4; D037102:Lectins; D037601:Mannose-Binding Lectin; D050606:Mannose-Binding Protein-Associated Serine Proteases; D011994:Recombinant Proteins; D000097604:Ficolins