| Project/Area Number |
13671604
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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 |
Anesthesiology/Resuscitation studies
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
SHIME Nobuaki Kyoto Prefectural University of Medicine, Medical school, Assistant professor, 医学部, 助手 (00260795)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Satoru Kyoto Prefectural University of Medicine, Medical school, Assocoate professor, 医学部, 助教授 (90167578)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Pseudomonas aeruginosa / Pneumonia / Sepsis / Type-III secresion / Neutralizing antibody / Therapy / 治療 / 特異的抗体 / ショック |
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| Research Abstract |
Pseudomonas aeruginosa lung infections are frequently associated with high mortality rates, particularly in patients receiving intensive care. Depending on the type III secretion phenotype, P. aeruginosa causes acute organ damage and septic physiology in P. aeruginosa lung infections. In this study, the effects of rabbit-derived polyclonal antibody against PcrV, a protein involved in the translocation of type III secreted toxins of Pseudomonas aeruginosa, was investigated in two animal models of P. aeruginosa sepsis. In a mouse survival study, the intravenous administration of anti-PcrV IgG after the airspace instillation of a lethal dose of P. aeruginosa resulted in the complete survival of the animals. In a rabbit model of septic shock associated with P. aeruginosa-induced lung injury, animals treated with anti-PcrV IgG intracheally or intravenously had significant decreases in lung injury, bacteremia, plasma TNF-α, and significant improvement in the hemodynamic parameters associated with shock compared to animals treated in a similar manner with non-specific control IgG. The administration of anti-PcrV F(ab')_2 showed protective effects comparable to whole anti-PcrV IgG. These results document that the therapeutic administration of anti-PcrV IgG blocks the type III secretion system-mediated virulence of P. aeruginosa and prevents septic shock and death, and that these protective effects are largely Fc-independent. We conclude that antibody therapy neutralizing the type III secretion system has significant potential against lethal P. aeruginosa infections
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