Cutting Edge: Role of MASP-3 in the Physiological Activation of Factor D of the Alternative Complement Pathway
Cutting Edge: Role of MASP-3 in the Physiological Activation of Factor D of the Alternative Complement Pathway
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DOI：
10.4049/jimmunol.1900605
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发表时间：
2019-09-15
影响因子：
4.4
通讯作者：
Sekine, Hideharu
中科院分区：
文献类型：
--
作者：
Hayashi, Manabu;Machida, Takeshi;Sekine, Hideharu
补体系统是先天免疫系统的一部分，可以通过三种不同的途径激活。在旁路途径中，因子D（FD）在起始和扩增环中起重要作用，并作为活性形式循环。甘露糖结合凝集素相关丝氨酸蛋白酶（MASP）是凝集素途径的关键酶，并且据报道MASP-1和/或MASP-3参与FD的活化。在本研究中，我们产生了MASP-1或MASP-3单特异性缺陷的小鼠，并发现MASP-1缺陷小鼠的血清缺乏凝集素途径活性，但MASP-3缺陷小鼠的血清缺乏酶原FD的替代途径活性。此外，结果表明MASP-3而不是MASP-1在生理条件下活化酶原FD，并且MASP-3主要作为活性形式循环。因此，我们的研究说明，在小鼠中，MASP-3通过FD的活化协调整体补体反应。
The complement system, a part of the innate immune system, can be activated via three different pathways. In the alternative pathway, a factor D (FD) plays essential roles in both the initiation and the amplification loop and circulates as an active form. Mannose-binding lectin-associated serine proteases (MASPs) are key enzymes of the lectin pathway, and MASP-1 and/or MASP-3 are reported to be involved in the activation of FD. In the current study, we generated mice mono-specifically deficient for MASP-1 or MASP-3 and found that the sera of the MASP-1-deficient mice lacked lectin pathway activity, but those of the MASP-3-deficient mice lacked alternative pathway activity with a zymogen FD. Furthermore, the results indicate that MASP-3 but not MASP-1 activates the zymogen FD under physiological conditions and MASP-3 circulates predominantly as an active form. Therefore, our study illustrates that, in mice, MASP-3 orchestrates the overall complement reaction through the activation of FD.