Elucidation of roles of platelet-activating factor receptor by gene targeting.

血小板活化因子（PAF）是一种有效的磷脂介质，参与炎症和过敏反应。研究还发现PAF在内毒素诱导的致死、生殖和脑发育中起重要作用。为了研究PAF及其受体在体内的作用，我们通过honorrhythmic重组建立了PAF受体缺陷小鼠。后代获得的孟德尔分布。它们正常生长，在检查的任何器官中均未观察到发育变化。血免疫球蛋白水平和细胞分类计数未见异常，卵蛋白致敏后，野生型小鼠出现明显的支气管收缩、肺水肿、低血压和死亡。另一方面，PAF受体缺陷小鼠对这些治疗仅表现出中度反应。在用内毒素挑战后，两组中未观察到显著差异。因此，我们得出结论，PAF深深参与过敏反应，而它在内毒素诱导的病理和致死性中显示出较小的作用。考虑到PAF受体拮抗剂对内毒素休克有一定的保护作用，即使在PAF受体敲除小鼠中，PAF受体拮抗剂可能还存在其他作用靶点，以保护机体免受内毒素休克的损害。

Platelet-activating factor (PAF) is a potent phospholipid mediator involved in inflammatory and allergic responses. It is also reported that PAF plays major roles in endotoxin-induced lethality, reproduction and brain development. To determine the role of PAF and its receptor in vivo, we generated a PAF receptor-deficient mice, by honologous recombination. Offspring were obtained with a Menderian distribution. They grow up normally, and no developmental changes are observed in any organs examined. The level of blood immunoglobulins and differential cell counts show no abnormality.When the mice were sensitized and challenged with ovalbumin, the wild type mice showed a marked bronchial constriction, pulmonary edema, hypotension and death. On the other hand, the PAF receptor-deficient mice showed only moderate response to these treatments. Upon challenging with endotoxin, no significant difference was observed in both groups. Thus, we concluded that PAF is deeply involved in anaphylactic responses, while it shows minor role in the endotoxin-induced pathologies and lethality. Considering PAF antagonists show some protective effects on endotoxin-shock, even in PAF receptor knock-out mice, there may exist other targets of PAF receptor antagonists to protect the living system from endotoxin-induced disorders.