Thiel S, Vorup-Jensen T, Stover C M, Schwaeble W, Laursen S B, Poulsen K, Willis A C, Eggleton P, Hansen S, Holmskov U, Reid K B, Jensenius J C
Department of Medical Microbiology and Immunology, University of Aarhus, Denmark.
Nature. 1997 Apr 3;386(6624):506-10. doi: 10.1038/386506a0.
The complement system comprises a complex array of enzymes and non-enzymatic proteins that is essential for the operation of the innate as well as the adaptive immune defence. The complement system can be activated in three ways: by the classical pathway which is initiated by antibody-antigen complexes, by the alternative pathway initiated by certain structures on microbial surfaces, and by an antibody-independent pathway that is initiated by the binding of mannan-binding lectin (MBL; first described as mannan-binding protein) to carbohydrates. MBL is structurally related to the complement C1 subcomponent, C1q, and seems to activate the complement system through an associated serine protease known as MASP (ref. 4) or p100 (ref. 5), which is similar to C1r and C1s of the classical pathway. MBL binds to specific carbohydrate structures found on the surface of a range of microorganisms, including bacteria, yeasts, parasitic protozoa and viruses, and exhibits antibacterial activity through killing mediated by the terminal, lytic complement components or by promoting phagocytosis. The level of MBL in plasma is genetically determined, and deficiency is associated with frequent infections in childhood, and possibly also in adults (for review, see ref. 6). We have now identified a new MBL-associated serine protease (MASP-2) which shows a striking homology with the previously reported MASP (MASP-1) and the two C1q-associated serine proteases C1r and C1s. Thus complement activation through MBL, like the classical pathway, involves two serine proteases and may antedate the development of the specific immune system of vertebrates.
补体系统由一系列复杂的酶和非酶蛋白组成，对于先天免疫和适应性免疫防御的运作至关重要。补体系统可通过三种方式激活：由抗体 - 抗原复合物启动的经典途径、由微生物表面某些结构启动的替代途径，以及由甘露聚糖结合凝集素（MBL；最初称为甘露聚糖结合蛋白）与碳水化合物结合启动的非抗体依赖性途径。MBL在结构上与补体C1亚成分C1q相关，似乎通过一种称为MASP（参考文献4）或p100（参考文献5）的相关丝氨酸蛋白酶激活补体系统，这与经典途径的C1r和C1s相似。MBL与一系列微生物表面发现的特定碳水化合物结构结合，包括细菌、酵母、寄生原生动物和病毒，并通过末端溶解补体成分介导的杀伤或促进吞噬作用表现出抗菌活性。血浆中MBL的水平由基因决定，其缺乏与儿童期频繁感染有关，在成人中可能也有关（综述见参考文献6）。我们现在鉴定出一种新的MBL相关丝氨酸蛋白酶（MASP - 2），它与先前报道的MASP（MASP - 1）以及两种C1q相关丝氨酸蛋白酶C1r和C1s具有显著同源性。因此，通过MBL激活补体，与经典途径一样，涉及两种丝氨酸蛋白酶，并且可能早于脊椎动物特异性免疫系统的发展。
