Lectin pathway effector enzyme mannan-binding lectin-associated serine protease-2 can activate native complement C3 in absence of C4 and/or C2
Lectin pathway effector enzyme mannan-binding lectin-associated serine protease-2 can activate native complement C3 in absence of C4 and/or C2
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DOI：
10.1096/fj.201601306r
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发表时间：
2017-05-01
期刊：
影响因子：
4.8
通讯作者：
Schwaeble, Wilhelm J.
中科院分区：
文献类型：
--
作者：
Yaseen, Sadam;Demopulos, Gregory;Schwaeble, Wilhelm J.
补体的所有3种活化途径-经典途径（CP）、旁路途径和凝集素途径（LP）-汇聚成一个共同的中心事件：通过形成C3活化酶（C3转化酶）裂解和活化丰富的第三补体成分C3。第四种补体成分C4和第二种成分C2是C3转化酶复合物C4 bC 2a的不可缺少的组成部分，该复合物由CP和LP形成。而在缺乏C4的情况下，CP不能再激活C3，LP保留了将天然C3转化为其激活片段C3 a和C3 b的残余但生理上关键的能力。这种残留的C4和/或C2旁路途径依赖于LP特异性甘露聚糖结合凝集素相关丝氨酸蛋白酶-2。通过使用具有确定的补体缺陷的各种血清来源，我们证明，在生理条件下，C3的LP特异性C4和/或C2旁路活化是通过与捕获在配体包被的表面上的LP活化复合物结合的甘露聚糖结合凝集素相关丝氨酸蛋白酶-2直接切割天然C3介导的。Yaseen，S.，Demopulos，G.，Dudler，T.，Yabuki，M.，伍德角L.，卡明斯，W。J.，乔尔克湖W.，藤田，T.，萨克斯，S.，Garred，P.，Andrew，P.，西姆河B.，Lachmann，P. J.，沃利斯河，林奇，纽约，Schwaeble，W. J.凝集素途径效应酶甘露聚糖结合凝集素相关丝氨酸蛋白酶-2可以在不存在C4和/或C2的情况下激活天然补体C3。
All 3 activation pathways of complement-the classic pathway (CP), the alternative pathway, and the lectin pathway (LP)-converge into a common central event: the cleavage and activation of the abundant third complement component, C3, via formation of C3-activating enzymes (C3 convertases). The fourth complement component, C4, and the second component, C2, are indispensable constituents of the C3 convertase complex, C4bC2a, which is formed by both the CP and the LP. Whereas in the absence of C4, CP can no longer activate C3, LP retains a residual but physiologically critical capacity to convert native C3 into its activation fragments, C3a and C3b. This residual C4 and/or C2 bypass route is dependent on LP-specific mannan-binding lectin-associated serine protease-2. By using various serum sources with defined complement deficiencies, we demonstrate that, under physiologic conditions LP-specific C4 and/or C2 bypass activation of C3 is mediated by direct cleavage of native C3 by mannan-binding lectin-associated serine protease-2 bound to LP-activation complexes captured on ligand-coated surfaces.-Yaseen, S., Demopulos, G., Dudler, T., Yabuki, M., Wood, C. L., Cummings, W. J., Tjoelker, L. W., Fujita, T., Sacks, S., Garred, P., Andrew, P., Sim, R. B., Lachmann, P. J., Wallis, R., Lynch, N., Schwaeble, W. J. Lectin pathway effector enzyme mannan-binding lectin-associated serine protease-2 can activate native complement C3 in absence of C4 and/or C2.