1999 Fiscal Year Final Research Report Summary
Study of Recognition/Response Mechanism of Macrophages to Pathogenic Microorganisms
Project/Area Number |
10670271
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Bacteriology (including Mycology)
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Research Institution | Showa University |
Principal Investigator |
YAMAGUCHI Koushi Showa University School of Medicine, Lecturer, 医学部, 講師 (70210359)
|
Co-Investigator(Kenkyū-buntansha) |
OKUBO Sachie Showa University School of Medicine, Lecturer, 医学部, 講師 (40053938)
|
Project Period (FY) |
1998 – 1999
|
Keywords | Macrophage / chemokine / scavenger receptor / immune response / cytokine / recognition |
Research Abstract |
It has been known that cytokines play an important role in the development of immunity and inflammatory responses. The project supported by the grant proposed to demonstrate an involvement of scavenger receptors in chemokine response of macrophages to microorganisms. In order to accomplish the purpose of the project, scavenger receptor inhibitors and scavenger receptor knock out mouse macrophages were utilized. The results showed that scavenger receptor inhibitors selectively inhibited the MIP-2 message induction of macrophages responded to Legionella pneumophila. Treatment of macrophages with clustered anti-class A scavenger receptor antibody to polymerize scavenger receptors showed an increased level of MIP-2 message. However, when class A scavenger receptor knock out mouse macrophages were tested, MIP-2 message was not induced by the clustered anti-class A scavenger receptor antibody. These results indicate that scavenger receptor may be involved in a certain chemokine induction. Wh
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en macrophages were treated with oxidized LDL, which binds to scavenger receptors, macrophage inflammatory protein 1 (MIP-1) and MIP-2 were markedly induced, but MCP-1 and lymphotactin were not. Treatment of macrophages with anti-scavenger receptor class A type I/II monoclonal antibody (2F8) to block the receptors inhibited the induction of MIP-1 and MIP-2 message by oxidized LDL. However, anti-MARCO (macrophage receptor with collagenous structure, other type of class A scavenger receptors) antibody inhibited only MIP-2 induction, but not MIP-1 message induction. The 2F8-conjugated latex beads stimulated macrophages to induce both MIP-1 and MIP-2 message. Furthermore, when class A scavenger receptor type I/II knock out mouse macrophages were stimulated with oxidized LDL, chemokine MIP-2 message was induced, but MIP-1 was not. These results indicate that scavenger receptors of macrophages may be selectively involved in the recognition and chemokine response of macrophages to microbial pathogens. Less
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