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

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），一种已知具有调理素和补体激活剂功能的动物凝集素，并建立了酶联免疫分析系统。使用该系统，我们测量了血清和几种体液中的MBP水平。对几种肾脏疾病的肾组织沉积物也进行了免疫荧光研究。1)分离得到的MBP纯度高，在SDS-PAGE上显示一条32 kD的单条带。然而，通过免疫程序分析，它与alpha_2-巨球蛋白（alpha_2-M）有关。2)用1085份年龄在3 ~ 100岁的日本人血清测定正常血清MBP水平。平均值在年轻人中最高（3-9岁，2.42马克杯/毫升），随着年龄的增长而下降。正常人血清整体平均值为1.72马克杯/毫升。3)出生时MBP水平约为1马克杯/毫升。从第2天开始急剧上升，并在出生后5天达到最高水平，相当于年轻人的水平。尿液、脑脊液和乳汁中MBP含量为血清水平的1/1000，表明大部分MBP存在于血清中。5)测定慢性和急性感染（包括结核病、HIV感染和先天性免疫缺陷）患者血清MBP水平。在慢性感染（如肺结核）中观察到显著增加的水平，但在艾滋病毒感染中没有。在先天性免疫缺陷中观察到类似的水平升高。6)狼疮性肾炎、膜性增殖性肾小球肾炎（I型）和IgA肾病患者肾小球均有MBP沉积。MBP的沉积与补体、C_1q和C_3的沉积平行，但与免疫球蛋白不平行，提示MBP参与补体沉积的发生。在本研究中，我们测定了日本人血清MBP的正常水平。血清MBP水平呈高度年龄依赖性。由于alpha_2-M对丝氨酸蛋白酶（如C_4转化酶）具有抑制活性，因此其与MBP制剂的关联可能为通过MBP调控补体活化提供了一种新的机制。MBP与补体成分在肾小球内的沉积提示存在一种新的肾沉积机制。少