Small mannose-binding lectin-associated protein plays a regulatory role in the lectin complement pathway
Small mannose-binding lectin-associated protein plays a regulatory role in the lectin complement pathway
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DOI：
10.4049/jimmunol.177.12.8626
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发表时间：
2006-12-15
影响因子：
4.4
通讯作者：
Fujita, Teizo
中科院分区：
文献类型：
--
作者：
Iwaki, Daisuke;Kanno, Kazuko;Fujita, Teizo
甘露糖结合凝集素(MBL)和甘露糖结合凝集素(Ficolins)是天然免疫中的模式识别蛋白，它们通过MBL相关丝氨酸蛋白酶(MASP)激活凝集素补体途径。当凝集素途径被激活时，MASP-2裂解C4和C2。MASP-2的一个截短形式，称为小MBL相关蛋白(SMAP)，也与MBL/斐果林-MASP复合体相关。为了阐明SMAP的作用，我们通过定向破坏SMAP特定的外显子来产生SMAP缺陷(SMAP(-/-))小鼠。由于基因突变，SMAP(-/-)小鼠MASP-2的表达水平也降低。当重组SMAP(RsMAP)和重组MASP-2(rMASP-2)在缺乏血清中重组MBL-MASP-SMAP复合体时，这些重组蛋白与MBL的结合是竞争性的，rMASP-2可恢复MBL-MASP-SMAP复合体的C4切割活性，而rsMAP的加入使其活性减弱。因此，MASP-2对C4的激活是必不可少的，SMAP在凝集素途径的激活中起着调节作用。
Mannose-binding lectin (MBL) and ficolins are pattern recognition proteins acting in innate immunity, and they trigger the activation of the lectin complement pathway through MBL-associated serine proteases (MASPs). Upon activation of the lectin pathway, MASP-2 cleaves C4 and C2. A truncated form of MASP-2, named small MBL-associated protein (sMAP), is also associated with MBL/ficolin-MASP complexes. To clarify the role of sMAP, we have generated sMAP-deficient (sMAP(-/-)) mice by targeted disruption of the sMAP-specific exon. Because of the gene disruption, the expression level of MASP-2 was also decreased in sMAP(-/-) mice. When recombinant sMAP (rsMAP) and recombinant MASP-2 (rMASP-2) reconstituted the MBL-MASP-sMAP complex in deficient serum, the binding of these recombinant proteins to MBL was competitive, and the C4 cleavage activity of the MBL-MASP-sMAP complex was restored by the addition of rMASP-2, whereas the addition of rsMAP attenuated the activity. Therefore, MASP-2 is essential for the activation of C4 and sMAP plays a regulatory role in the activation of the lectin pathway.