1990 Fiscal Year Final Research Report Summary
Novel bioactions of platelet-activating factor (PAF)
| Project/Area Number |
63571035
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KUDO Ichiro Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (30134612)
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| Co-Investigator(Kenkyū-buntansha) |
ARAI Hiroyuki Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (40167987)
UMEDA Masato Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (10185069)
INOUE Keizo Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (30072937)
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| Project Period (FY) |
1988 – 1990
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| Keywords | platelet-activating factor / cytokines / M-CSF / TNF / bone marrow cells / cell proliferation / differentiation / Candida parapsilosis |
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| Research Abstract |
(1) PAF-specific binding sites with high affinity were found on guinea pig bone marrow cells. When guinea pig bone marrow cells were incubated in the presence of PAF, microbicidal activity against Candida parapsilosis of cells was augmented. This augmentation was inhibited by PAF-specific antagonist, CV6209 or FR900452. Carrageenan or 2-choloroadenosine, reagents known to be preferentially cytotoxic to macrophages, abolished the microbicidal activity. Thus, PAF may affect a class of guinea pig bone marrow cells through binding to receptors specific to PAF, resulting in activation and/or inducton of differentiation of monocyte-macrophage lineage cells.
(2) When guinea pig bone marrow cells were incubated in the presence of PAF, an incorporation of radioactive thymidine into cells were time-dependently augmented. This augmentation was abolished by specific PAF antagonists, CV-6209 or FR900452. When the conditioned medium of PAF-stimulated bone marrow cells was added to another culture of
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bone marrow cells, the augmentation of DNA synthesis was also observed. Thus, PAF may affect the proliferation of one or some classes of guinea pig bone marrow cells through release of soluble factors. Anti-mouse TNF antibody or anti-human M-CSF antibody partially inhibited the DNA synthesis induced by PAF, suggesting the production and involvement of guinea pig TNF and M-CSF in this PAF bioaction.
(3) The addition of conditioned medium of PAF-treated bone marrow cells augmented not only the DNA synthesis but the induction of microbicidal activity.
(4) Upon stimulation with TNF, an appreciable amount of PAF was produced in guinea pig stromal cells. When treated with PAF, bone marrow cells generated an appreciable amount of TNF. Therefore, TNF and PAF induces generation of each other in bone marrow. This network would lead to enormous augmentation of the PAF bioaction in bone marrow.
(5) Prostaglandin E2 inhibits DNA synthesis induced by PAF. The inhibitory effect was vary potent ; its ID50 value was about 3 x 10^<-10> M. Less
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