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

血清甘露聚糖结合蛋白（MBP）是一种针对甘露糖/ n-乙酰氨基葡萄糖胺的c型动物凝集素，已从多种哺乳动物血清中分离得到。MBP是胶原样凝集素的一员，在疾病或感染早期的一线宿主防御中起重要作用。为了阐明MBP在血清水平上广泛的内部和不同种族差异的机制，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，称为“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开始的转录子比从外显子0开始的转录子占优势。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从外显子1上调人MBP的转录，而已知上调急性期蛋白的糖皮质激素（glucocorti…More coid）则显著抑制MBP的转录。最近，据报道，低血清MBP浓度与常见的听觉缺陷有关，并引起婴儿频繁的不明原因感染。这些患者在胶原样区域的密码子52、54或57突变为同源或杂合，并阻止了MBP高寡聚物的组装。一项种群研究也表明，听觉缺陷的频率几乎与突变等位基因的频率相对应。我们研究了正常和Gly54到Asp突变的MBPs在小鼠血浆中的代谢特性。发现放射性标记的正常MBP的半衰期约为6小时，而突变MBP的半衰期几乎为其一半。这些结果部分解释了突变体MBP.3的低血清浓度。最近，在启动子区域的两个位置发现了多态性。功能启动子分析表明，这些位点的3个单倍型变异HY、LY和LX分别表现出高、中、低启动子活性，与先前的群体研究结果一致。少

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