Human serum mannose-binding protein: its function and a possible application to the clinical use.
Grant-in-Aid for General Scientific Research (B)
|Allocation Type||Single-year Grants|
|Research Institution||Hokkaido University|
KOBAYASHI Kunihiko Hokkaido University School of Medicine, Professor, 医学部, 教授 (60091451)
|Project Period (FY)
1991 – 1992
Completed(Fiscal Year 1992)
|Budget Amount *help
¥6,600,000 (Direct Cost : ¥6,600,000)
Fiscal Year 1992 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1991 : ¥5,400,000 (Direct Cost : ¥5,400,000)
|Keywords||mannose-binding protein / MBP / lectin / acute phase protein / complement / alpha_2-macroglobulin / MBP(mannose bincling pnotein) / 急性反応性蛋白 / マンノ-ス結合蛋白 / MBP(mannose binding protein) / α_2ーmacroglbulin|
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.
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
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