2012年11月9日 讯 /生物谷BIOON/ --近日，来自丹麦奥胡斯大学的科学家与来自美国、土耳其的研究者合作研究，发现了一种机体免疫功能的重要分子机制，相关研究成果刊登于国际杂志Journal of Immunology上。在文章中，研究者发现了酶类在免疫防御第一道防线中发挥作用的分子机制，这就回答了关于补体系统的一个重要问题。
通过对罕见遗传综合征病人血样的分析，研究者揭示出了酶MASP-1是补体系统激活的一个关键酶类。研究者表示，一旦我们知道了补体系统如何进行“工作”，那么我们就有可能人为控制它；比如说这个系统对于目前正在研究化疗病人的生存来说非常重要，因为疗法会抑制病人机体免疫系统其它功能的发挥，然而当前的研究发现并不能给出一个合理疗法的建议。
此前研究中，研究者发现了四种和MASP-1相关的蛋白质，为MASP-2、MASP-3、MAp19和MAp-44，这些蛋白质作为外源凝集素途径的重要组分构成了激活补体路径的中央部分。
酶MASP-1可以有效地自我激活，比如当其感知到细菌后，随后就可以激活MASP-2，紧接着就会以级联效应的方式激活补体系统的其余组分，此后该系统中的一系列酶类就可以互相进行激活，发挥作用。结果就是免疫系统会接收到信号，对入侵的细菌进行杀灭。补体系统也可以通过在细菌细胞膜上形成类似核心的结构来在细菌表面进行穿孔，杀灭细菌。（生物谷Bioon.com）
编译自：New Immune Pathway Discovered
doi:10.4049/jimmunol.1201736
PMC:
PMID:
Mannan-Binding Lectin-Associated Serine Protease (MASP)-1 Is Crucial for Lectin Pathway Activation in Human Serum, whereas neither MASP-1 nor MASP-3 Is Required for Alternative Pathway Function
Søren E. Degn*, Lisbeth Jensen*, Annette G. Hansen*, Duygu Duman†, Mustafa Tekin†‡§, Jens C. Jensenius* and Steffen Thiel*
The lectin pathway of complement is an important component of innate immunity. Its activation has been thought to occur via recognition of pathogens by mannan-binding lectin (MBL) or ficolins in complex with MBL-associated serine protease (MASP)-2, followed by MASP-2 autoactivation and cleavage of C4 and C2 generating the C3 convertase. MASP-1 and MASP-3 are related proteases found in similar complexes. MASP-1 has been shown to aid MASP-2 convertase generation by auxiliary C2 cleavage. In mice, MASP-1 and MASP-3 have been reported to be central also to alternative pathway function through activation of profactor D and factor B. In this study, we present functional studies based on a patient harboring a nonsense mutation in the common part of the MASP1 gene and hence deficient in both MASP-1 and MASP-3. Surprisingly, we find that the alternative pathway in this patient functions normally, and is unaffected by reconstitution with MASP-1 and MASP-3. Conversely, we find that the patient has a nonfunctional lectin pathway, which can be restored by MASP-1, implying that this component is crucial for complement activation. We show that, although MASP-2 is able to autoactivate under artificial conditions, MASP-1 dramatically increases lectin pathway activity at physiological conditions through direct activation of MASP-2. We further demonstrate that MASP-1 and MASP-2 can associate in the same MBL complex, and that such cocomplexes are found in serum, providing a scenario for transactivation of MASP-2. Hence, in functional terms, it appears that MASP-1 and MASP-2 act in a manner analogous to that of C1r and C1s of the classical pathway.
