| Project/Area Number |
14570225
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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 |
寄生虫学(含医用動物学)
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| Research Institution | Fujita Health University |
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Principal Investigator |
MAENO Yoshimasa Fujita Health Univetsity, School of Medicine, Associate Professor, 医学部, 助教授 (70131191)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Jun Fujita Health Uuiversity, School of Medicine, Assistant Preofessor, 医学部, 講師 (70319268)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Malaria / Osteopontin / Th1-mediated immunity / Malaria granuloma / IL-12 / IFN-γ / Macrophage / Neuroglia cell / 熱帯熱マラリア / 脳マラリア / TNF-alha / ベトナム / マラリアグラニュローマ / RT-PCR / IL-12 / IFN-gamma / ネズミマラリア / 一酸化窒素 / ノックアウトマウス |
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| Research Abstract |
No studies on osteopontin (OPN) function have been performed for malaria infection. By using Osteopontin knockout (OPN-KO) mice with a resistant C57BL/6 background, in this study, we examined whether or not infection by P. c. chabaudi induces OPN production and how OPN is involved in the control of malaria parasites. OPN-KO mice died of Plasmodium chabaudi chabaudi infection although wild type (WT) mice showed self-limiting infection. OPN was detected in the WT mice after two days postinfection. OPN-KO mice produced significantly lower amounts of interleukin-12 (IL-12) and interferon-γ (IFN-γ) than WT ones did.
Next step, we examined the role of osteopontin (OPN) in immunity against Plasmodium falciparum infection. We measured the mRNA levels for OPN and several cytokines in RNA preparations extracted from dried blood oat filter paper obtained from falcipatum malaria patients in Vietnam. Expression of OPN mRNA was detected in 134 of 161 patients. The expression of both IL-12 p40 and IFN-γ mRNAs in the group positive for OPN mRNA was higher than that in the group negative for OPN mRNA. The level of parasitemia in the OPN mRNA-positive group was lower than that in the negative one. These results suggest that OPN might suppress multiplication of the parasites through T helper 1 cells-mediated immune responses.
Malaria granuloma is one of histopathological changes in the brain tissues of cerebral malaria (CM). OPN-positive cells were histochemically observed in all the postmortem brain sections from CM patients and were localized both in the granulomas and in perivascular sites. OPN was detected in macrophages/monocytes and neuroglia cells. Tumor necrosis factor (TNF)-α was stained in the matrix of perivascular sites of microvessels with sequestered parasitized erythriocytes. These results imply that OPN may be involved in pathogenesis of CM and may contribute to formation of malaria granulomas.
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