2012年11月9日 訊 /生物谷BIOON/ --近日,，來自丹麥奧胡斯大學的科學家與來自美國,、土耳其的研究者合作研究，發(fā)現了一種機體免疫功能的重要分子機制,，相關研究成果刊登于國際雜志Journal of Immunology上,。在文章中，研究者發(fā)現了酶類在免疫防御第一道防線中發(fā)揮作用的分子機制,，這就回答了關于補體系統(tǒng)的一個重要問題,。
通過對罕見遺傳綜合征病人血樣的分析,，研究者揭示出了酶MASP-1是補體系統(tǒng)激活的一個關鍵酶類。研究者表示,，一旦我們知道了補體系統(tǒng)如何進行“工作”,，那么我們就有可能人為控制它,；比如說這個系統(tǒng)對于目前正在研究化療病人的生存來說非常重要，因為療法會抑制病人機體免疫系統(tǒng)其它功能的發(fā)揮,，然而當前的研究發(fā)現并不能給出一個合理療法的建議,。
此前研究中,，研究者發(fā)現了四種和MASP-1相關的蛋白質,，為MASP-2,、MASP-3,、MAp19和MAp-44,，這些蛋白質作為外源凝集素途徑的重要組分構成了激活補體路徑的中央部分,。
酶MASP-1可以有效地自我激活,，比如當其感知到細菌后，隨后就可以激活MASP-2,，緊接著就會以級聯效應的方式激活補體系統(tǒng)的其余組分，此后該系統(tǒng)中的一系列酶類就可以互相進行激活,，發(fā)揮作用,。結果就是免疫系統(tǒng)會接收到信號,，對入侵的細菌進行殺滅。補體系統(tǒng)也可以通過在細菌細胞膜上形成類似核心的結構來在細菌表面進行穿孔,，殺滅細菌,。（生物谷Bioon.com）
編譯自：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.
