Mechanisms of mannose-binding lectin-associated serine proteases-1/3 activation of the alternative pathway of complement.
Mechanisms of mannose-binding lectin-associated serine proteases-1/3 activation of the alternative pathway of complement.
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甘露糖结合凝集素相关的丝氨酸蛋白酶1/3的机理的补体途径激活。
DOI：
10.1016/j.molimm.2011.08.021
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发表时间：
2011-10
影响因子：
3.6
通讯作者：
Arend WP
中科院分区：
文献类型：
--
作者：
Banda NK;Takahashi M;Takahashi K;Stahl GL;Hyatt S;Glogowska M;Wiles TA;Endo Y;Fujita T;Holers VM;Arend WP
甘露糖结合凝集素相关丝氨酸蛋白酶-1/3（MASP-1/3）通过将前因子D（pro-Df）切割成成熟Df而在激活补体的旁路途径（AP）中是必需的。据信MASP需要结合甘露糖结合凝集素（MBL）或纤维胶凝蛋白（FCN）以实现其生物活性。据报道，鼠血清含有MBL-A、MBL-C和FCN-A，但不含有内源性存在于单核细胞中且被认为不结合MASP-1的FCN-B。我们研究了MASP-1/3可能激活AP的一些可能机制。胶原抗体诱导的关节炎是一种依赖于AP的炎性关节炎小鼠模型，与野生型小鼠相比，缺乏MBL-A、MBL-C和FCN-A的小鼠（MBL−/−/FCNA −/−小鼠）的关节炎没有变化。使用MBL−/−/FCN A−/−小鼠血清，粘附于胶原II的mAb对AP的体外诱导是完整的。此外，来自MBL−/−/FCN A−/−小鼠的血清缺乏前Df，仅具有成熟Df。来自MBL−/−/FCN A−/−小鼠的血清的凝胶过滤显示MASP-1蛋白存在于含有比来自C4−/−小鼠的血清中的MBL-A和MBL-C的迁移更小的蛋白的级分中，这表明MASP-1可能与未知蛋白结合。最后，我们发现FCN-B存在于MBL−/−/FCN A−/−小鼠的血清中，并且与MASP-1结合。我们得出结论，MASP-1不需要结合MBL-A、MBL-C或FCN-A来激活AP。MASP-1可通过与FCN-B或未知蛋白结合将pro-Df切割成成熟Df，或可作为未结合的可溶性蛋白发挥功能。
Mannose-binding lectin-associated serine proteases-1/3 (MASP-1/3) are essential in activating the alternative pathway (AP) of complement through cleaving pro-factor D (pro-Df) into mature Df. MASP are believed to require binding to mannose binding lectins (MBL) or ficolins (FCN) to carry out their biological activities. Murine sera have been reported to contain MBL-A, MBL-C, and FCN-A, but not FCN-B that exists endogenously in monocytes and is thought not to bind MASP-1. We examined some possible mechanisms whereby MASP-1/3 might activate the AP. Collagen antibody-induced arthritis, a murine model of inflammatory arthritis dependent on the AP, was unchanged in mice lacking MBL-A, MBL-C, and FCN-A (MBL−/−/FCN A−/− mice) in comparison to wild-type mice. The in vitro induction of the AP by adherent mAb to collagen II was intact using sera from MBL−/−/FCN A−/− mice. Furthermore, sera from MBL−/−/FCN A−/− mice lacked pro-Df and possessed only mature Df. Gel filtration of sera from MBL−/−/FCN A−/− mice showed the presence of MASP-1 protein in fractions containing proteins smaller than the migration of MBL-A and MBL-C in sera from C4−/− mice, suggesting possible binding of MASP-1 to an unknown protein. Lastly, we show that FCN-B was present in the sera of MBL−/−/FCN A−/−mice and that it was bound to MASP-1. We conclude that MASP-1 does not require binding to MBL-A, MBL-C, or FCN-A to activate the AP. MASP-1 may cleave pro-Df into mature Df through binding to FCN-B or to an unknown protein, or may function as an unbound soluble protein.
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影响因子：
3.2
作者：
Motomura, Wataru;Yoshizaki, Takayuki;Wakamiya, Nobutaka
通讯作者：
Wakamiya, Nobutaka
影响因子：
4.6
作者：
Banda, N. K.;Levitt, B.;Arend, W. P.
通讯作者：
Arend, W. P.
影响因子：
4.4
作者：
Banda, Nirmal K.;Takahashi, Kazue;Arend, William P.
通讯作者：
Arend, William P.
影响因子：
5.3
作者：
Harboe M;Mollnes TE
通讯作者：
Mollnes TE
影响因子：
56.9
作者：
Forneris, Federico;Ricklin, Daniel;Gros, Piet
通讯作者：
Gros, Piet