Studies on Sugar Recognition by Animal Lectins

血清甘露聚糖结合蛋白（MBP）是一种C-型凝集素，它与以甘露糖或N-乙酰葡糖胺残基为末端的糖链结合。一旦MBP与固体支持物（如细菌细胞）上的配体糖结合，它就通过称为“凝集素途径”的新途径激活补体。这种凝集素的生理意义通过发现血清中缺乏凝集素的患者患有严重的感染性疾病而清楚地证明。在过去的一年中，我们通过对人MBP基因5'上游启动子活性的分析，研究了MBP mRNA的表达机制。将5'上游区基因片段-845/+69插入到含荧光素酶基因的报告质粒中，该片段除含有基本启动子元件CAAT和TATA盒外，还含有多个共有序列。用IL 6、TNF-α、INF-γ和佛波酯（PMA）等细胞因子处理HepG 2细胞后，荧光素酶的表达水平无明显变化，而地塞米松则抑制荧光素酶的表达，使其降低到对照组的一半。MBP基因5'上游区的逐步缺失导致表达的上调和下调，表明在该启动子区存在多个负和正调控元件。

Serum mannan-binding protein (MBP) is a C-type lectin which binds to sugar chains terminated with mannose or N-acetylglucosamine residue. Once MBP binds to ligand sugars on a solid support such as bacterial cells, it activates complement through a new pathway called "lectin pathway". The physiological significance of this lectin was demonstrated clearly by the finding that the patients deficient of the lectin in their serum suffer from serious infectious diseases. In the past one year, we have studied the mechanism of the expression of MBP mRNA by analyzing promoter activity of the 5' upstream region of human MBP gene. 5' upstream region gene fragment -845/+69, which contains several consensus sequences in addition to basic promoter elements CAAT and TATA boxes, was inserted into reporter plasmid containing luciferase gene. The resultant construct was transfected into Hep G2 cells, which was shown to express MBP mRNA.Treatment of the transfected cells with cytokines such as IL6, TNF-a, INF-g and PMA (phorbol 12-myristate 13-acetate) did not show any significant effects on the level of expression of luciferase, while dexamethasone inhibited the expression to one half the control level. Step wise deletions of the MBP gene from 5' upstream region resulted in the up and down regulation of the expression suggesting the presence of multiple negative and positive regulatory elements in this promoter regions.