Novel bioactions of platelet-activating factor (PAF)

(1)在豚鼠骨髓细胞上发现了高亲和力的PAF特异性结合部位。当豚鼠骨髓细胞与PAF共同孵育时，细胞对近缘念珠菌的杀灭活性增强。PAF特异性拮抗剂CV6209或FR900452可抑制这种增强作用。卡拉胶或2-氯腺苷是已知的对巨噬细胞具有优先细胞毒性的试剂，它们取消了杀菌活性。因此，PAF可能通过与PAF特异性受体结合而影响一类豚鼠骨髓细胞，从而激活和/或诱导单核巨噬细胞系细胞分化。(2)当豚鼠骨髓细胞与PAF共同孵育时，放射性胸腺嘧啶核苷的掺入呈时间依赖性增加。这种增强作用可被特定的PAF拮抗剂CV-6209或FR900452消除。将经PAF刺激的骨髓细胞的条件培养液加入另一种…培养中骨髓细胞增多，DNA合成增强。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。抗小鼠肿瘤坏死因子抗体或抗人M-CSF抗体部分抑制PAF诱导的DNA合成，提示豚鼠TNF和M-CSF参与了PAF的这一生物学作用。(3)加入经PAF处理的骨髓细胞的条件培养液不仅能促进DNA合成，而且能诱导杀菌活性。(4)经肿瘤坏死因子刺激后，豚鼠骨髓基质细胞产生大量PAF。当用PAF处理时，骨髓细胞产生了相当数量的肿瘤坏死因子。因此，肿瘤坏死因子和纤溶酶原激活剂在骨髓中相互诱导生成。这种网络将导致PAF在骨髓中的生物活性大大增强。(5)前列腺素E2抑制PAF诱导的DNA合成。抑制作用不同，其ID_(50)值约为3×10~(-10)×10~(-5)M。

(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