Human serum mannose-binding protein: its function and a possible application to the clinical use.

人血清甘露糖结合蛋白：其功能和临床应用的可能。

基本信息

批准号：
03454505
负责人：
KOBAYASHI Kunihiko
金额：
$ 4.22万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

We isolated mannose-binding protein(MBP), an animal lectin known to function as opsonin and complement activator, from human serum and developed an enzyme-linked immunoassay system. Using this system, we measured levels of MBP in serum and several body-fluids. Immunofluorescence study was also carried out for deposits of renal tissues from several renal diseases.1)The isolated MBP was pure showing a single band on SDS-PAGE at 32 kD. However, it was associated with alpha_2-macroglobulin (alpha_2-M) when analyzed by immunological procedures.2)Normal serum MBP levels were determined using a total of 1085 Japanese sera ranging in age from 3 to 100 year-old. The mean value was highest in younger people(3-9 Y, 2.42mug/ml) and it declined in accord with age. The mean value of normal human serum as a whole was 1.72 mug/ml.3)The MBP level at birth was around 1 mug/ml. It elevated abruptly from day 2 and reached the highest level, equivalent to that of younger people, in 5 days after birth.4)Bod … More y-fluids including urine, cerebrospinal fluids and milk had MBP at 1/1000 of serum level, indicating that most of MBP reside in serum.5)Serum levels of MBP were determined for chronic and acute infections, including tuberculosis, HIV infections and congenital immunodeficiencies. A significant increased level was seen in chronic infections such as tuberculosis but not in HIV infections. A similar increased level was observed in congenital immunodeficiencies.6)Deposition of MBP in renal glomerulus was detected in lupus nephritis, membranous proliferative glomerular nephritis(type I) and IgA nephropathy. The deposition of MBP was parallel to that of complements, C_1q and C_3, but not to immunoglobulins, suggesting the involvement of MBP in the occurrence of complement deposition.In the present study, we determined normal levels of serum MBP in Japanese. The high age-dependency was present in the serum MBP level. The association of alpha_2-Min the MBP preparation might give rise to a novel mechanism in the regulation of complement activation through MBP, since the alpha_2-M has inhibitory activity for serine protease, such as C_4 convertase. Deposition of MBP in renal glomerulus together with complement components suggests the presence of a new mechanisms in the occurrence of renal deposition. Less

我们从人血清中分离出甘露糖结合蛋白（MBP）是一种被称为Opsonin和补体激活剂的动物讲座，并开发了一种酶联免疫测定系统。使用该系统，我们测量了血清和几种身体流体的MBP水平。还对几种肾脏疾病的肾脏组织沉积进行了免疫荧光研究。1）纯净的MBP纯净显示在32 kd时SDS-PAGE上的单个条带。然而，当通过免疫学分析时，它与α_2-摩ac蛋白（alpha_2-m）有关。2）使用总共1085个日本血清范围从3至100岁的年龄确定了正常的血清MBP水平。年轻人（3-9 y，2.42mug/ml）的平均值最高，并且根据年龄的增长下降。正常人血清的平均值为1.72mug/ml.3）出生时的MBP水平约为1 mug/ml。它从第2天开始突然升高，并达到最高水平，等同于年轻人，在出生后的5天内。先天性免疫缺陷。在慢性感染（例如结核病）但没有在HIV感染中观察到显着升高。在先天性免疫缺陷中观察到了类似的水平。6）MBP在肾小球肾炎，膜增生剂肾小球肾炎（I型）和IGA肾病中检测到MBP的沉积。 MBP的沉积与C_1Q和C_3的完成平行，但不与免疫球蛋白的沉积，这表明MBP参与完成沉积。在本研究中，我们确定了日语中血清MBP的正常水平。高年龄依赖性在血清MBP水平上存在。 Alpha_2-MIN的关联MBP制剂可能会引起通过MBP调节完成激活的新机制，因为Alpha_2-M具有抑制丝氨酸蛋白酶的抑制活性，例如C_4转化酶。 MBP在肾肾小球中的沉积以及完成成分的沉积表明在肾脏沉积发生时存在一种新机制。较少的