Cultured endothelial cells synthesize both platelet-activating factor and prostacyclin in response to histamine, bradykinin, and adenosine triphosphate.

Cultured endothelial cells synthesize both platelet-activating factor and prostacyclin in response to histamine, bradykinin, and adenosine triphosphate.
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培养的内皮细胞响应组胺、缓激肽和三磷酸腺苷合成血小板激活因子和前列环素。

DOI:
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发表时间:
1985
影响因子:
15.9
通讯作者:
Nora Eccles
Nora Eccles
中科院分区:
医学1区
文献类型:
--
作者:
T. M. Mcintyre;Guy;A.;Zimmerman;Kei Satoh;S. Prescott;Nora Eccles

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当用组胺、缓激肽或 ATP 刺激时,培养的人内皮细胞会合成前列环素 (PGI2),这是一种有效的血小板功能抑制剂。矛盾的是,我们报告这些激动剂还诱导内皮细胞快速持续地合成血小板激活因子(PAF)。事实上,这种有效的血小板和中性粒细胞激活剂的合成是通过刺激诱导 PGI2 合成的相同受体亚型来诱导的:刺激组胺 H1 或缓激肽 B2 受体可诱导 PAF 和 PGI2 合成。然而,内皮细胞产生的 PAF 和 PGI2 之间存在两个生理上重要的差异。 PGI2 的合成仅进行了 7.5 分钟,然后合成突然终止,而 PAF 的合成甚至在刺激后 45 分钟仍可清晰检测到。虽然 PAF 的最大积累发生在刺激 10-15 分钟后,但长时间的合成导致刺激后 PAF 存在长达 1 小时。其次,虽然 PGI2 从细胞单层释放,但 PAF 仍然与细胞相关,没有显着释放到外部介质中。因此,内皮细胞产生的 PAF 不具有激素的功能。这种血小板和中性粒细胞的有效激活剂与内皮细胞的长期结合可能介导组胺和缓激肽的一些炎症特性。它也可能是血栓形成血管表面形成的一个因素,这一事件被认为在血栓形成和动脉粥样硬化的发病机制中起主要作用。
Cultured human endothelial cells synthesize prostacyclin (PGI2), a potent inhibitor of platelet function, when stimulated with histamine, bradykinin, or ATP. Paradoxically, we report that these agonists also induced the rapid and sustained synthesis of platelet-activating factor (PAF) by endothelial cells. In fact, the synthesis of this potent activator of platelets and neutrophils was induced by stimulation of the same receptor subtype that induced PGI2 synthesis: stimulation of a histamine H1 or a bradykinin B2 receptor induced both PAF and PGI2 synthesis. However, two physiologically important differences exist between the production of PAF and PGI2 by endothelial cells. The synthesis of PGI2 proceeded for only 7.5 min before the abrupt termination of synthesis, whereas the synthesis of PAF was clearly detectable even 45 min after stimulation. Although maximal accumulation of PAF occurred after 10-15 min of stimulation, the prolonged synthesis resulted in the presence of PAF for up to 1 h after stimulation. Secondly, whereas PGI2 was released from the cell monolayer, PAF remained cell-associated without significant release to the external medium. Endothelial cell-generated PAF, therefore, does not function as a hormone. The prolonged association of this potent activator of platelets and neutrophils with endothelial cells may mediate some of the inflammatory properties of histamine and bradykinin. It may also be a factor in the formation of a thrombogenic vascular surface, an event suggested to play a primary role in the pathogenesis of thrombosis and atherosclerosis.
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DOI: 10.1073/pnas.80.13.4109
发表时间: 1983
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