1988 Fiscal Year Final Research Report Summary
Role of sugar chain in the induction of Fc receptor-mediated phagocytosis by macrophages
| Project/Area Number |
62580109
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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 |
物質生物化学
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| Research Institution | the University of Tokyo |
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Principal Investigator |
TAKASAKI Seiichi the Institute of Medical Science, the University of Tokyo, 医科学研究所, 助教授 (80112093)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Fc receptor-mediated phagocytosis / High mannose-type sugar chain / プロセシング阻害剤 |
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| Research Abstract |
Phagocytosis can be separated into two steps, attachment of the foreign material to the cell membrane and ingestion of the material. A mouse macrophage-like cell line, P388Dl, expresses receptors which recognize Fc portion of IgG bound to antigen, but can not take up the antigen-antibody conplex. However, addition of dimethyl sulfoxide (DMSO) toe the culture medium induces the ability of ingestion in more than 90% of the cells after 2 days. It is known that structural changes are accompanied with macrophage differentiation. Therefore, sugar chain structures were compared before and after DMSO induction of P388DL cells, and the relationship between structural changes and induction of Fc receptor-mediated phagocytosis was studied in this project. Finally, the following results were obtained. (1) From the analysis of NP-40 extracts of the cells by SDS-PAGE, it was obvious that the total protein pattern does not change after DMSO induction. But, increased staining by Concanavalin A of glyc
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oproteins with molecular sizes of more than 30 KDa was observed after induction. (2) After DMSO induction, high mannose-type sugar chains increased with the decrease of tri- and tetraantennary complex-type sugar chains. Thus, the data suggestd that inhibition of the processing of ASN-linked sugar chains is involved in the structural change caused by DMSO induction. (3) When the cells were cultured in the presence of processing inhibitors (swainsonine and castanospermine), which accumulate high mannose-type sugar chains, Fc receptor-mediated phagocytosis was induced depending on the dose of inhibitors and the culture time.
These results indicate that structural change of sugar chains is not merely accompanied with the induction, but causes the induction of Fc receptor-mediated phagocytosis. Expression of high mannose-type sguar chains in some specific glycoproteins might be a key for the induction, suggesting that it is important to analyze the mechanism of induction on the molecular basis in the near future. Less
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