Mannose-binding lectin (MBL)-associated serine protease (MASP)-1 contributes to activation of the lectin complement pathway
Mannose-binding lectin (MBL)-associated serine protease (MASP)-1 contributes to activation of the lectin complement pathway
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DOI：
10.4049/jimmunol.180.9.6132
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发表时间：
2008-05-01
影响因子：
4.4
通讯作者：
Fujita, Teizo
中科院分区：
文献类型：
--
作者：
Takahashi, Minoru;Iwaki, Daisuke;Fujita, Teizo
补体系统在天然免疫中起重要作用。在凝集素补体途径中，甘露糖结合凝集素（MBL）和纤维胶凝蛋白（ficolins）起识别分子的作用，而MBL相关丝氨酸蛋白酶（MASP）是关键酶。已经表明MASP-2负责C4的活化。其他丝氨酸蛋白酶（MASP-1和MASP-3）也与MBL或纤维胶凝蛋白相关;然而，它们的功能仍有争议。在本研究中，通过基因靶向策略产生MASP-1和MASP-3缺陷型小鼠模型（MASP 1/3（-/-））以研究MASP-1和MASP-3在凝集素途径中的作用。来自MASP 1/3（-/-）小鼠的血清显示出C4和C3在甘露聚糖-琼脂糖上沉积的显著较低活性，并且通过添加重组MASP-1恢复了该低活性。与正常血清相比，MASP-1/3缺陷型血清显示MASP-2活化的显著延迟。重组MASP-1在MASP-1/3缺陷型血清中的重构能够促进MASP-2的活化。从这些结果，我们提出MASP-I有助于凝集素途径的活化，可能通过MASP-2的活化。
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-I contributes to the activation of the lectin pathway, probably through the activation of MASP-2.