The lectin complement pathway is involved in activation of the alternative pathway

凝集素补体途径参与旁路途径的激活

• 批准号: 21390086
• 负责人: FUJITA Teizo
• 金额: $ 10.65万
• 依托单位: Fukushima Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390086/
• 关键词: 免疫学; 自然免疫; 補体; レクチン経路; 第2経路; MASP; 感染症; 生体分子; 糖鎖; 凝固系

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 thought to be a key enzyme that cleaves C4 and C2 to assemble a C3 convertase(C4b2a). However, a 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 mouse model, and found that the deficient mice lacked alternative pathway activation, because 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-3 was able to activate Bf of the alternative pathway. Thus, MASP-1 and MASP-3 seems to be involved in activation of both the lectin and alternative pathways, thereby, playing a central role in innate immunity.

在凝集素途径中，甘露糖结合凝集素（MBL）和纤维蛋白充当病原体的模式识别分子，从而激活了与MBL相关的丝氨酸蛋白酶（MASPS; MASPS; MASP-1，MASP-2，MASP-2和MASP-3）的激活。在这些蛋白酶中，MASP-2被认为是裂解C4和C2以组装C3转化酶（C4B2A）的关键酶。但是，MASP-1和MASP-3的生理功能尚不清楚。为了研究MASP-1和MASP-3的作用，我们生成了MASP-1和MASP-3缺陷小鼠模型，发现缺乏小鼠缺乏替代途径激活，因为DF仍是血清中的蛋白酶。 MASP-1和MASP-3能够在体外转化为活性形式。此外，MASP-3能够激活替代途径的BF。因此，MASP-1和MASP-3似乎参与了凝集素和替代途径的激活，从而在先天免疫中起着核心作用。

项目成果

Contributions of MASP-1 and MASP-3 to fat metabolism by activation of complement factor D.

MASP-1 和 MASP-3 通过激活补体因子 D 对脂肪代谢的贡献。

• 发表时间: 2009
• 作者: Liu M;他3名;武川睦寛;Sato H;藤田禎三
• 通讯作者: 藤田禎三

The role of ficolins in the lectin pathway of innate immunity

• DOI: 10.1016/j.biocel.2011.02.003
• 发表时间: 2011-05-01
• 期刊: INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
• 影响因子: 4
• 作者: Endo, Yuichi;Matsushita, Misao;Fujita, Teizo
• 通讯作者: Fujita, Teizo

The Role of Mannose-Binding Lectin-Associated Serine Protease-3 in Activation of the Alternative Complement Pathway

• DOI: 10.4049/jimmunol.1100280
• 发表时间: 2011-10-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Iwaki, Daisuke;Kanno, Kazuko;Fujita, Teizo
• 通讯作者: Fujita, Teizo

Essential role of mannose-binding lectin-associated serine protease-l in activation of the complement factor D

甘露糖结合凝集素相关丝氨酸蛋白酶-1 在补体因子 D 激活中的重要作用

• 发表时间: 2010
• 期刊: J Exp Med
• 影响因子: 15.3
• 作者: Takahashi M;Ishida Y;Iwaki D;Kan no K;Suzuki T;Endo Y;Homma Y;and Fujita T.
• 通讯作者: and Fujita T.

L-Ficolin Binds to the Glycoproteins Hemagglutinin and Neuraminidase and Inhibits Influenza A Virus Infection Both in vitro and in vivo

• DOI: 10.1159/000335670
• 发表时间: 2012-01-01
• 期刊: JOURNAL OF INNATE IMMUNITY
• 影响因子: 5.3
• 作者: Pan, Qin;Chen, Haidan;Zhang, Xiao-Lian
• 通讯作者: Zhang, Xiao-Lian