1988 Fiscal Year Final Research Report Summary
Studies on the complement activation by human serum lectin.
| Project/Area Number |
62570983
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
KAWASAKI Nobuko Kyoto University, College of Medical Technology, 医療技術短期大学部, 助教授 (70077676)
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| Co-Investigator(Kenkyū-buntansha) |
KAWASAKI Toshisuke Kyoto University, Faculty of Pharmaceutical Sciences, 薬学部, 助教授 (50025706)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Mannan-binding Protein / Carbohydrate-binding Protein / Serum Lectin / Complement / Bactericidal Activity / Mammalian Lectin / Classical Pathway / 生体防御 |
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| Research Abstract |
Human serum mannan-binding protein (MBP), which is a lectin specific for mannose and N-acetylglucosamine, was shown to lyse mannan-coated SRBC with the help of human complement. The activation by erum MBP was inhibited effectively by the presence of haptenic sugars and dependent absolutely upon the presence of C4, indicating that the actaivation is initiated by the sugar binding activity of MBP and proceeds through the classical pathway. ^<125>I-labeled C1r^^-_2s^^-_2 was shown to bind to MBP-mannan-SRBC complex regardless of the presence of C1q-depleted human complement had an ability to support to lyse SRBC sensitized with MBP, suggesting that MBP, once fixed on cell surfaces, functions as C1q does to initiate the activation of the classical pathway.
The bacteria, rugh strains of Escherichia coli, K-12 and B, which had been sensitized with purified human serum MBP in the presence of CA^<2+>, followed by incubation with guinea pig complement, showed a marked decrease of colony forming
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ability compared with those not sensitized with the lectin. The bactericidal effect depended on the concentrations of the lectin and complement. The C4-dependency of the reaction indicated that the complement-dependent bactericidal action by MBP is expressed through the classical pathway. The bacteria were aggregated by MBP. Scatchard polt analysis of ^<125>I-labeled BMP binding to the bacteria showed that the dissociation constant (K_d) and the maximum binding capacity was 6x10<@1-9<@D1M and 30,000 molecules of MBP per a cell, respectively. The binding was inhibited by mannose, N-acetylglucosamine, suggesting that MBP recognized mannoheptose and N-acetylgucosamine constituting the rough core oligosaccharides of the bacterial cell wall.
Thus, MBP-ligand (the bacteria) complex activates complement via the classical pathway possibly through the binding directly to C1r^^-_2s^^-_2 without the involvement of C1q and eventually the bacteria are killed. These findings demonstrate the physiological significance of the serum lectin in host defense, being consistent with the avirulence of E.coli rough strains in mammals. Less
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Research Products
(10 results)
