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* Department of Immunology, Fukushima Medical University School of Medicine, Fukushima,
Institute of Glycotechnology and Department of Applied Biochemistry, Tokai University, Hiratsuka, and
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan; and
Department of Immunology and Laboratory of Allergy and Clinical Immunology, Institute of Allergy and Immune-related Diseases and Medical Research Center, Wuhan University School of Medicine, Wuhan, China
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.
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1 This work was supported by Grant-in-Aids (11770078, 13770072, and 17790327) for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by Core Research for Evolutional, Science, and Technology, Japan Science and Technology Agency.
2 Address correspondence and reprint requests to Dr. Teizo Fujita, Department of Immunology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, Japan. E-mail address: tfujita{at}fmu.ac.jp
3 Abbreviations used in this paper: MBL, mannose-binding lectin; MASP, MBL-associated serine protease; ES, embryonic stem; sMAP, small MBL-assocaited protein; rMASP-1n, recombinant native type of MASP-1; rMASP-1i, recombinant inactive MASP-1 mutant; rMASP-1K, recombinant MASP-1 mutant modified by replacing the arginine429 with lysine; rMASP-2i, recombinant inactive MASP-2 mutant.
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