1994 Fiscal Year Final Research Report Summary
Elucidation of the Mechanism for Macrophage Activation induced by Liposomes
| Project/Area Number |
05671848
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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 | Tokyo University of Pharmacy and Life Science, School of Pharmacy |
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Principal Investigator |
ARAMAKI Yukihiko Tokyo Univ.of Pharmacy and Life Science, School of Pharmacy, Associate Professor, 薬学部, 助教授 (90138959)
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| Project Period (FY) |
1993 – 1994
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| Keywords | liposome / macrophage / Fc-receptor / alpha2-macroglobulin |
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| Research Abstract |
Elucidation of the mechanism for macrophage activation induced by liposomes was investigated in mice by measuring the phagocytosis of IgG-opsonized sheep red blood cells (SRBC) via Fc receptor of mouse peritoneal macrophages as a index of activation, and the following findings were obtained ; 1)Macrophages were activated by activating factor identified as modified alpha2-macrogloburin (alpha-MG), but not liposomes directly, 2)Modified alpha-MG having mannose residue at the terminal of sugar chain was generated from alpha-MG by the action of glycosidases, galactosidase and glucosaminidase, of liposomes treated B-cells, 3)B-cell membranous glycosidases were activated by the addition of liposomes, and this activation was inhibited by anti-IgM antibody, suggesting that the activation of B-cell galactosidase and glucosaminidase induced by liposomes was regulated by B-cell surface IgM (sIgM). 4)By immunoprecipitation with anti-IgM antibody and B-cell lysate, the both enzyme activities were recovered in the same precipitin of IgM,indicating that galactosidase and glucosaminidase were localized in plasma membrane of B-cells associating with sIgM,5)Macrophage activation induced by modified alpha-MG was inhibited by addition of mannose, suggesting that modified alpha-MG binds to mannose-receptor of macrophage and activates macrophage to phagocyte opsonized SRBC through Fc-receptor.
From above findings, the mechanism of macrophage activation by liposomes is considered as follows : liposomes interact with B-cells through sIgM and activate membranous glycosidases which are associated with sIgM.Activated glycosidases hydrolyze galactose and glucosamin residues of alpha-MG and generate modified alpha-MG having mannose residue at the terminal of sugar chain. The modified alpha-MG interact with mannose-receptor of macrophage and activate macrophage to phagocyte IgG-opsonized SRBC via Fc-receptor.
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