| Project/Area Number |
08670329
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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 | NATIONA INSTITUTE OF HEALTH SCIENCES |
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Principal Investigator |
TANAMOTO Ken-ichi National Institute of Health Sciences, Bacteriology, Head, 衛生微生物部, 室長 (60107430)
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| Co-Investigator(Kenkyū-buntansha) |
HAISHIMA Yuji National Institute of Health Sciences, Bacteriology, 衛生微生物部, 室長 (80228379)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | endotoxin / lipid A / antagonist / Porphyromonas gingivalis / C3H / HeJ mice / TNF-alpha / サクシニル化 |
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| Research Abstract |
The lipid A from Porphyromonas gingivalis, which we recently isolated and whose complete chemical structure was determined, exhibited endotoxic activity in all the assay systems tested. The activity was, however, much more moderate than that of Salmonella minnesota LPS used as a control (about 100-fold less).The lipid A was found to induce splenocyte mitogenicity and TNF- alpha release from peritoneal macrophages in LPS-unresponsive C3H/HeJ mice to the same extent as in LPS-responsive mice. In order to clarify whether the activation of C3H/HeJ mice was specifically caused by the lipid A and not by contaminating protein, two strategies were employed. The lipid A fraction from P.gingivalis was subjected to either hydrochloric acid or alkaline treatment, to eliminate either glycosylated phosphate or 0-acylated fatty acids from the lipid A structure, and the biological activities of the derivatives were compared in both LPS-responsive and unresponsive C3H/HeJ mice. De-1-O-phosphorylated P.
… More
gingivalis lipid A showed partial loss, and de-O-acylated lipid A complete loss of splenocyte mitogenic and TNF- alpha inductive activities from peritoneal macrophages in both LPS-responsive and unresponsive mice. The relative activities of the intact and treated lipid A compounds in splenocyte mitogenicity and TNF- alpha inductive activity in macrophages were similar to the relative activities of these preparations in Limulus gelation activities. The LPS-specific antagonist, succinylated lipid A precursor, inhibited P.gingivalis lipid A-mediated splenocyte mitogenicity and TNF-alpha induction in macrophages in a similar manner in LPS-responsive and unresponsive mice. These results strongly suggest that the activation of LPS-unresponsive C3H/HeJ mice by P.gingivalis lipid A was specifically mediated by the lipid A portion and not by contaminating protein. The characteristic action of P.gingivalis lipid A on LPS-unresponsive C3H/HeJ mice was thought to reflect the unique chemical properties of this compound. Less
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