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Novel bioactions of platelet-activating factor (PAF)

血小板活化因子（PAF）的新生物作用

基本信息

批准号：
63571035
负责人：
KUDO Ichiro
金额：
$ 1.47万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1990
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63571035/
关键词：
platelet-activating factor cytokines M-CSF TNF bone marrow cells cell proliferation differentiation Candida parapsilosis

项目摘要

(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 … More 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

(1)在豚鼠骨髓细胞上发现了PAF特异性结合位点。当豚鼠骨髓细胞在PAF存在下孵育时，细胞对近平滑念珠菌的杀微生物活性增强。PAF特异性拮抗剂CV 6209或FR 900452可抑制这种增强作用。卡拉胶或2-chloroadenosine，试剂已知是优先细胞毒性的巨噬细胞，废除了杀微生物活性。因此，PAF可能通过与PAF特异性受体结合来影响一类豚鼠骨髓细胞，导致单核细胞-巨噬细胞谱系细胞的激活和/或诱导分化。(2)当豚鼠骨髓细胞在PAF存在下孵育时，放射性胸苷掺入细胞中呈时间依赖性增加。这种增强作用被特异性PAF拮抗剂CV-6209或FR 900452消除。当PAF刺激的骨髓细胞的条件培养基加入到另一种培养物中时， ...更多信息骨髓细胞，DNA合成的增加也被观察到。因此，PAF可能通过释放可溶性因子影响一种或几种豚鼠骨髓细胞的增殖。抗小鼠TNF抗体或抗人M-CSF抗体可部分抑制PAF诱导的DNA合成，提示TNF和M-CSF的产生参与了PAF的生物学作用。(3)PAF处理的骨髓细胞的条件培养基的加入不仅增强了DNA合成，但杀菌活性的诱导。(4)在TNF刺激下，豚鼠基质细胞产生可观量的PAF。当用PAF处理时，骨髓细胞产生可观量的TNF。因此，TNF和PAF在骨髓中相互诱导产生。这个网络将导致PAF在骨髓中的生物作用的巨大增强。(5)前列腺素E2抑制PAF诱导的DNA合成。其抑制作用是不同强度的;其ID 50值约为3 × 104 μ <-10>M。少