2000 Fiscal Year Final Research Report Summary
Studies on effector molecules of innate immunity responsible for cytotoxicity to tumor cells.
| Project/Area Number |
10470478
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
NAGASAWA Shigeharu Hokkaido Univ.Grad.Sch.Pharm.Sci., Pro., 大学院・薬学研究科, 教授 (70029958)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Yusuke Hokkaido Univ.Grad.Sch.Pharm.Sci., Inst., 大学院・薬学研究科, 助手 (10250466)
YAMASHITA Toshiyuki Hokkaido Univ.Grad.Sch.Pharm.Sci., Lec., 大学院・薬学研究科, 講師 (90192400)
TAKAHASHI Kazuhiko Hokkaido Univ.Grad.Sch.Pharm.Sci., Asso.Pro., 大学院・薬学研究科, 助教授 (10113581)
SEYA Tsukasa Osaka Med.Cent.Cancer and Cardiovas.Diseases, Div.Head., 部長 (10301805)
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| Project Period (FY) |
1998 – 2000
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| Keywords | sulfatides / neutrophils / tumor cells / phagocytosis / complement / M.fermentans / apoptosis / EF-1α |
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| Research Abstract |
A.Enhancement of CR3-mediated neutrophil phagocytosis by sulfatides.
Sulfatides is a ligand for L-selectin and triggers intracellular signals in human neutrophils. We found for the first time the enhancement of CR3-mediated human neutrophil phagocytosis by sulfatides. FcR-mediated phagocytosis was not modified by sulfatides treatment We also observed that unidentified receptor for sulfatides exists on human neutrophils and participates in the enhancement of phagocytosis.
B.Homologous complement activators expressed on apoptotic and malignant cells.
a ; Apoptotic as well as native T cells were found to contain a homologous complement activator of 50 kDa. Amino acid seqenece analysis was identical to those of elongation factor 1α. The homologous complement activator activity was removed with anti-EF-1α.
b. We found a M161Ag, which is expressed on human malignant cells and induces homologous complement activation. cDNA of M161Ag revealed that it is highly homologous to P48, mycoplasma fermentans gene product. It was revealed that latently infected M.fermentans allows human cells to produce M161Ag, which is a potent modulator of innate and cellular immune responses via its complement activating and cytokine-producing activity.
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[Publications] Begum, N.A., Murakami, Y., Matsumoto, M., Hatanaka, M., Nagasawa, S., Kinoshita, T., & Seya, T.: "Molecular remodeling of human CD46 for xenotransplantation ; designing a potent complement regulator without measles virus receptor activity."Immunology. 99. 1-13 (2000)
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[Publications] Murakami, Y., Fukui, A., Seya, T., Ueda, S., & Nagasawa, S.: "Effect of mutations at the residues R25, D27, P69 and N70 of B95a-MCP on receptor activities for the measles viruses Nagahata wild-type strain and CAM vaccine strain."Inter.J.Molec.Med.. 3. 25-32 (1999)
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[Publications] Seya, T., Nomura, M., Murakami, Y., Begum, N.A., Matsumoto, M., & Nagasawa, S.: "CD46 (membrane cofactor protein of complement, measles virus receptor) : structural and functional divergence among species (Review)""Inter.J.Mol.Med.. 1. 809-816 (1998)
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[Publications] Mikata, S., Miyagawa, S., Fukui, A., Murakami, Y., Shirakura, R., Matsuda, H., Hatanaka, M., Matsumoto, M., Seya, T., Suzuki, K., & Nagasawa, S.: "A monomeric human C4b-binding protein (C4bp) more efficiently inactivates C3b than natural C4bp ; participation of C-terminal domains in factor l-cofactor activity."Molec.Immunol.. 35. 537-544 (1998)
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[Publications] Matsumoto, M., Nishiguchi, M., Kikkawa, S., Nishimura, H., Nagasawa, S., and Seya, T.: "Structural and functional properties of complement-activating protein M161Ag, a micoplasma fermentans gene product that induces cytokine production by human monocytes."J.Biol.Chem.. 273. 12407-12414 (1998)
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