| Project/Area Number |
12670239
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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 | Dokkyo University School of Medicine |
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Principal Investigator |
KAWAI Satoru Dokkyo university school of medicine, Dep. of Tropical Medicine and Parasitology, Assistant Professor, 医学部, 講師 (70275733)
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| Co-Investigator(Kenkyū-buntansha) |
TERAO Keiji The National Institute of Infectious Diseases Tsukuba Primate Center for Medical Science, Director, 筑波医学実験用霊長類センター, センター長 (30109920)
MATSUMOTO Jun Dokkyo university school of medicine, Dep. of Tropical Medicine and Parasitology, Research Associate, 医学部, 助手 (70296169)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Severe malaria / primate model / Japanese macaque / T cell / apoptosis / TUNEL staining / soluble Fas ligand / MMPI / Fas抗原 |
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| Research Abstract |
The asexual stage of the simian malaria parasite, Plasmodium coatneyi (CDC strain), was intravenously inoculated into two species of macaques with different susceptibilities to infection with this parasite, Japanese macaques (Macaca fuscata) and cynomolgus macaques (M. fascicularis). The Japanese macaques infected with P. coatneyi developed severe clinical manifestations similar to those of severe human malaria, while the infected cynomolgus macaques, exhibited no severe manifestation of disease except anemia, and finally recovered from the infection. In the infected Japanese macaques, peripheral CD4^+ and CD8^+ T-cell populations were markedly decreased and fragmentation of chromosomal DNA in peripheral blood mononuclear cells was detected during the terminal period of infection, suggesting that apoptotic cell death was responsible for the T lymphocytopenia. Furthermore, soluble Fas ligand level in serum of the infected Japanese macaques increased gradually to a markedly high level when they became moribund. On the other hand, none of the infected cynomolgus monkeys exhibited either T lymphocytopenia or the elevation of soluble Fas ligand level. These findings suggest that differences in immune response between the two species of macaque tested accounted for the contrasting outcomes after infection with the same isolate of malarial parasite, and in particular that a profound T lymphocytopenia due to Fas-derived apoptosis played a role in the fatal course of malaria in the infected Japanese macaques.
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