Department of Immunology, Fukushima Medical University School of Medicine, Fukushima City, Fukushima 960-1295, Japan.
Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima City, Fukushima 960-1295, Japan.
J Immunol. 2019 Sep 15;203(6):1411-1416. doi: 10.4049/jimmunol.1900605. Epub 2019 Aug 9.
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 monospecifically 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.
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被激活。在替代途径中，一种因子 D（FD）在起始和放大环中都起着至关重要的作用，并以活性形式循环。甘露聚糖结合凝集素相关丝氨酸蛋白酶（MASPs）是凝集素途径的关键酶，有报道称 MASP-1 和/或 MASP-3 参与 FD 的激活。在本研究中，我们生成了 MASPs-1 或 MASPs-3 特异性缺失的小鼠，并发现 MASPs-1 缺失小鼠的血清缺乏凝集素途径活性，但 MASPs-3 缺失小鼠的血清缺乏 FD 酶原的替代途径活性。此外，结果表明，在生理条件下，MASP-3 而非 MASP-1 激活 FD 酶原，并且 MASP-3 主要以活性形式循环。因此，我们的研究表明，在小鼠中，MASP-3 通过 FD 的激活来协调整体补体反应。
