Healing of several PAF-derived diseases by newly disigned PAF antagonists

1.本项目的组织者Waku研究了人嗜酸性粒细胞中血小板活化因子(PAF)的产生和释放。A 23187激活的低密度嗜酸性粒细胞产生PAF的强度是正常嗜酸性粒细胞的3-4倍，并能很容易地从嗜酸性粒细胞中释放PAF。本文还研究了人嗜酸性粒细胞产生超氧阴离子(O_2)的能力，并与中性粒细胞产生超氧阴离子(O_2)进行了比较。结论：1.人嗜酸性粒细胞在PAF刺激下产生(O_2)的能力是中性粒细胞的4-5倍，提示嗜酸性粒细胞对肺细胞的损伤可能是由于PAF刺激产生的超氧阴离子所致。Nojima通过给兔注射二甲基氨基甲酰-CPGPC制备了PAF抗体。该抗体能强烈抑制MBBIT的血小板凝集作用，对PAF引起的失血性休克有保护作用。井上已证实，注射PAF激动剂对X射线照射所致的小鼠中性粒细胞减少有保护作用。这些结果表明PAF对小鼠骨髓中性粒细胞的增殖有促进作用。小林新设计了含有双环化合物的PAF拮抗剂，其效果是标准PAF拮抗剂CV-3988的10倍。这些新设计的PAF拮抗剂有望对嗜酸性粒细胞的PAF受体起到非常有效的作用。

1. Waku, the organizer of this project, studied the production and release of Platelet Activa% Factor(PAF)in the human eosinophils. The A 23187-activated hypodense eosinophils could produce PAF 3-4 times more strongly than the normodence eosinophils and could easily release PAF from the eosinophil cells. The production of superoxide anion(O_2)by the human eosinophils is also studied in comparison with that of human neutrophils. The human eosinophds could produce(O_2)4-5 times more strongly than the human neutrophits on the stimulation by PAF and these results suggest du the damage of lung celts by eosinophils may be due to the strong production of this superoxide anion by the stimulation of PAF.2. Nojima has prepared the PAF antibody by injecting dimethylcarbamoyl-CPGPC to rabbit. This antibody strongly suppressed the platelet coagulation of mbbit and may be useful for protecting animals from the anapbylactic shock caused by PAF.3. Inoue has demo d that the decrease of number of mouse neutrophils by X-ray irradiation was protected by injecdag PAF agonist to the mouse. These results show the role of PAF for the proliferation of neutrophffs in mouse bone marrow.4. Kobayashi has newly designed the PAF antagonist having bicyclo compounds, which is 10 times more effective as an PAF antgonist than the standard PAF antagonist, CV-3988. It is hoped that these newly designed PAF antagonist could be very effective to the PAF receptor of eosinophils.