Department of Immunology, Fukushima Medical University School of Medicine, 1-Hikariga-oka, Fukushima 960-1295, Japan.
Adv Exp Med Biol. 2013;735:41-53. doi: 10.1007/978-1-4614-4118-2_3.
The complement system, which consists of more than 30 plasma and cell surface proteins, is activated by three pathways: the classical, lectin, and alternative pathways, leading to the generation of opsonins and pathogen destruction. 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 a key enzyme that cleaves C4 and C2 to assemble a C3 convertase (C4b2a). However, the 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 (M1/3 KO) mouse model and found that the deficient mice lacked alternative pathway activation because factor D (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-1 was able to activate MASP-2 and MASP-3 as C1r activates C1s. Thus, MASP-1 and MASP-3 seem to be involved in activation of both the lectin and alternative pathways.
补体系统由超过 30 种血浆和细胞表面蛋白组成，通过三种途径激活：经典途径、凝集素途径和替代途径，导致调理素和病原体的破坏。在凝集素途径中，甘露糖结合凝集素 (MBL) 和纤维胶凝素作为病原体的模式识别分子，导致 MBL 相关丝氨酸蛋白酶 (MASPs: MASP-1、MASP-2 和 MASP-3) 的激活。在这些蛋白酶中，MASP-2 是一种关键酶，可裂解 C4 和 C2 以组装 C3 转化酶 (C4b2a)。然而，MASP-1 和 MASP-3 的生理功能仍不清楚。为了研究 MASP-1 和 MASP-3 的作用，我们生成了 MASP-1 和 MASP-3 缺陷型 (M1/3 KO) 小鼠模型，发现缺陷型小鼠缺乏替代途径激活，因为因子 D (Df) 在血清中仍然是一种酶原。MASP-1 和 MASP-3 能够在体外将 Df 的酶原转化为活性形式。此外，MASP-1 能够像 C1r 激活 C1s 一样激活 MASP-2 和 MASP-3。因此，MASP-1 和 MASP-3 似乎参与了凝集素途径和替代途径的激活。
