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Mannan结合蛋白（MBP）是一种针对甘露糖/N-乙酰葡萄糖的C型动物讲座，已从各种哺乳动物血清中分离出来。 MBP是收集素（胶原蛋白样讲座）的成员，在疾病或感染的早期阶段，在一线宿主防御中起着重要作用。1。为了阐明在MBP血清水平上广泛的异族种类的机制，我们研究了人MBP的转录调节。 HEP G2 RNA的cDNA末端分析的快速扩增表明存在一种新型外显子，称为“外显子0”，这是先前鉴定的外显子上游。 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急性相蛋白，明显抑制MBP转录2。最近，据报道，低血清MBP浓度与常见的Opsonic缺陷有关，并导致婴儿经常引起意外感染。患者在类似胶原蛋白的区域的密码子52、54或57突变中是同性或杂合的，并防止了MBP较高的寡寡糖组装。一项人口研究还表明，Opsonic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GLY54对ASP突变体Mbps的代谢特性。发现放射性标记的正常MBP的半衰期约为6H，而突变体MBP的半衰期几乎是一半。这些结果部分解释了突变体MBP的串行浓度低3。最近，发现在两个位置的启动子区域中发生了多态性。功能启动子分析表明，根据先前的人群研究的结果，分别对这些位置的三种单倍型变体分别暴露了高，中和低启动子活性。较少的