权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Regulation of the Serum Level of the Collectins Associated with Host Defense

与宿主防御相关的集合素血清水平的调节

基本信息

批准号：
09672223
负责人：
KAWASAKI Nobuko
金额：
$ 1.98万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

Serum mannan-binding protein (MBP), a C-type animal lectin specific for mannose/N-acethylglucosamine, has been isolated from various mammalian sera. MBP is a member of the collectin (collagen-like lectin) and plays an important role in the first-line host defense during the early stage of a disease or infection.1. In order to elucidate the mechanism underlying the wide intra-and interracial variety in the MBP serum level, we have studied the transcriptional regulation of human MBP. Rapid amplification of cDNA ends analysis of Hep G2 RNA indicated the presence of a novel exon, designated as "exon 0", upstream of previously identified exon. Promoter analysis involving a luciferase assay vector revealed that the tran-script starting from exon 1 predominates over that starting from exon 0. In addition, a hepatocyte-specific nuclear factor (HNF)-3, which is known to control the expression of hepatocyte-specific genes, upreulates the transcription of human MBP from exon 1, while a glucocorti … More coid, which is known to upregulate acute phase proteins, markedly suppresses MBP transcription.2. Recently, it was reported that a low serum MBP concentration is associated with a common opsonic defect and causes frequent unexplained infections in infants. The patients were homo-or heterozygous for a codon 52, 54 or 57 mutation in the collagen-like region and prevents the assembly of MBP higher oligo-mers. A population study has also shown that the frequency of the opsonic defect nearly corresponds to that of mutant alleles. We studied the metabolic properties of the normal and Gly54 to Asp mutant MBPs in mouse plasma. The radiolabeled normal MBP was found to have a half-life of about 6h, while that of the mutant MBP was almost half as long. These results explain in part the low serum concentration of the mutant MBP.3. Recently, polymorphisms were found to occur in the promoter region at two positions. Functional promoter analysis indicated that three haplotype variants as to these positions, HY, LY and LX, exhibit high, medium and low promoter activity, respectively, in accordance with the results of a previous population study. Less

血清甘露聚糖结合蛋白（MBP）是一种对甘露糖/N-乙酰氨基葡萄糖具有特异性的C型动物凝集素，已从多种哺乳动物血清中分离得到。MBP是胶原样凝集素（collagen-like lectin）的一员，在疾病或感染的早期，在宿主的第一线防御中发挥重要作用.为了阐明MBP血清水平的广泛种族内和种族间差异的机制，我们研究了人类MBP的转录调控。Hep G2 RNA的cDNA末端快速扩增分析表明，在先前鉴定的外显子上游存在一个新的外显子，命名为“外显子0”。涉及荧光素酶测定载体的启动子分析显示，从外显子1开始的转录物比从外显子0开始的转录物占优势。此外，已知控制肝细胞特异性基因表达的肝细胞特异性核因子（HNF）-3上调人类MBP外显子1的转录，而葡萄糖皮质激素（glucocorti）则上调人类MBP外显子1的转录。 ...更多信息已知coid可上调急性期蛋白，显著抑制MBP的转录。最近，据报道，低血清MBP浓度与常见的调理素缺陷有关，并导致婴儿频繁发生不明原因的感染。这些患者在胶原蛋白样区域中的密码子52、54或57突变是纯合或杂合的，并且阻止了MBP高聚体的组装。一项群体研究也表明，调理素缺陷的频率几乎与突变等位基因的频率相对应。我们研究了小鼠血浆中正常和Gly 54到Asp突变的MBP的代谢特性。放射性标记的正常MBP的半衰期约为6小时，而突变MBP的半衰期几乎是其一半。这些结果部分解释了突变MBP的低血清浓度。最近，多态性被发现发生在启动子区的两个位置。功能性启动子分析表明，三个单倍型变体，这些位置，HY，LY和LX，表现出高，中，低启动子活性，分别与以前的人口研究的结果。少