2000 Fiscal Year Final Research Report Summary
Role of scavenger receptor in the processing of bacterial antigens
| Project/Area Number |
11670208
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | NIIGATA UNIVERSITY |
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Principal Investigator |
NAITO Makoto School of Medicine, NIIGATA UNIVERSITY, Professor, 医学部, 教授 (30045786)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Takashi School of Medicine, NIIGATA UNIVERSITY, Assistant, 医学部, 助手 (70313517)
HASEGAWA Go School of Medicine, NIIGATA UNIVERSITY, Lecturer, 医学部, 講師 (90251800)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Scavenger receptor / knockout mice / endotoxin shock / macrophages / listeria / granuloma / host defense / MARCO |
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| Research Abstract |
Type I and type II macrophage scavenger receptors (MSR-A I/II) recognize a variety of polyanions including bacterial cell wall products such as lipopolysaccharide. suggesting a role for MSR-A I/II in immunity against bacterial infection.
In the first study, we used mice lacking the MSR-A to elucidate the role of MSR-A in endotoxin shock. Peritoneal macrophages from MSR-A-deficient (MSR-A-/-) mice bound less remarkably to LPS than those from wild type (MSR-A+/+) mice. Clearance of LPS in serum was retarded in MSR-A-/- mice after intraperitoneal administration of LPS, suggesting that MSR-A function as a receptor for LPS.LPS-induced expressions of IL-1 βwere lower in MSR-A-/- than MSR-A+/+ mice.
Administration of large doses of LPS resulted in a higher mortality of MSR-A+/+ than of MSR-A-/- mice, and pretreatment with an IL-1 receptor antagonist reduced the mortality.
In the second study, we clarified that MSR-A-/- mice were more susceptible to infection with listeriolysin-O (LLO)-producing listeria monocytogenes. After infection, Kupffer cells in wild type (MSR-A+/+) mice phagocytized larger numbers of Listeria than those in MSR-A-/- mice. Listeria monocytogenes replicated at higher levels in the liver of MSR-A-/- mice compared with MSR-A+/+ mice, and macrophages from MSR-A-/- mice showed impaired ability to kill listeria in vitro. SR-A I/II function as a receptor for L.monocytogenes. Electron microscopic observation on the intracytoplasmic behavior of bacteria revealed that SR-A I/II plays a crucial role in host defense against listerial infection not only by functioning as a receptor but also by mediating listericidal mechanisms through the regulation of LLO-dependent listerial escape from the macrophages.
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Research Products
(16 results)
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[Publications] Kobayashi Y, Miyaji C, Watanabe H, Umezu H, Hasegawa G, Abo T, Arakawa M, Kamata N, Suzuki H, Kodama T, Naito M: "Role of macrophage scavenger receptor in endotoxin shock."J Pathol. 192. 263-272 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Ito S, Naito M, Kobayashi Y, Takatsuka H, Jiang S, Usuda H, Umezu H, Hasegawa G, Arakawa M, Shultz LD, Elomaa O, Tryggvason K: "Roles of macrophage receptor with collagenous structure (MARCO) in host defense and heterogeneity of splenic marginal zone macrophages."Arch Histol Cytol. 62(1). 83-95 (1999)
Description
「研究成果報告書概要(欧文)」より
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