| Project/Area Number |
09670295
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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 |
Bacteriology (including Mycology)
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| Research Institution | Jichi Medical School |
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Principal Investigator |
MATSUURA Motohiro Jichi Medical School, Medical Department, Associate Professor, 医学部, 助教授 (20150089)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Shinji Jichi Medical School, Medical Department, Research Associate, 医学部, 助手 (50195989)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Endotoxin / Lipopolysaccharide / LPS / Lipid A / TNF / IL-6 / Human macrophages / リボ多糖 / リポ多糖(LPS) / TNF-α |
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| Research Abstract |
The lipid A portion of bacterial LPS plays a central role in the production of endotoxic mediators. Different responses between human and murine macrophages to lipid A-like structures have been indicated. We investigated a series of structurally related monosaccharide lipid A analogues for their potency to activate human macrophage U937 cells and peripheral blood mononuclear cells for production of TNF-alpha and IL-6 compared with that of murine macrophage RAW264.7 cells. As the results, it was reveal that the structure of lipid A analogues recognized as LPS agonist by human cells comprises D-glucosamine, phosphoryl groups and acyl groups with defined carbon chain lengths of C14 and C12 in a ratio proportional to 1 : 1 : 3 ; these constituents are common to monosaccharide and disaccharide molecules and the elements necessary for recognition are more strict than those required by murine cells. In contrast, broad lipid A-like structures, which are recognized by the murine cells as LPS agonist and antagonist, are recognized as being LPS antagonist by human cells. It is now an important subject in LPS studies to find and characterize a putative LPS-receptor which transduces LPS-signals into cells. It is proposed that the protein recognizes lipid A-like structures in a productive or nonproductive manner for signal transduction and that the difference in this protein between animal species causes species specificity in the response of the cells to lipid A-like structures. In the present study, such a protein can be assumed to play a role as the target molecule for lipid A analogues to transduce their signals as LPS agonist or antagonist. Based on the information obtained in this study, further application of monosaccharide lipid A analogues as well as disaccharide analogues is promising in the search for valuable new information to elucidate of such problems.
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