Unidirectional transfer of prostaglandin endoperoxides between platelets and endothelial cells.
Unidirectional transfer of prostaglandin endoperoxides between platelets and endothelial cells.
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前列腺素内过氧化物在血小板和内皮细胞之间的单向转移。
DOI：
10.1172/jci111296
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
GimbroneJr,MA
中科院分区：
文献类型：
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作者：
Schafer,AI;Crawford,DD;GimbroneJr,MA
血小板-血管壁相互作用的一个重要决定因素是内皮前列环素 (PGI2) 和血小板血栓素 (TX) A2 的产生的局部平衡，这两种不稳定的类二十烷酸对止血具有相反的作用。有争议的证据表明，血小板衍生的前列腺素内过氧化物中间体可用作血管 PGI2 合成的底物。使用几种不同的方法，我们发现血小板可以将内过氧化物转移到培养的内皮细胞以有效转化为PGI2，但在相同的实验条件下不会发生内皮内过氧化物被血小板血栓素合成酶利用的相互转移。然而，血小板可以利用内皮细胞释放的花生四烯酸进行脂氧合酶代谢。我们直接证明了在[3H]花生四烯酸刺激的血小板存在下，阿司匹林处理的内皮细胞可产生[3H]6-酮-PGF1α（[3H]PGI2的分解产物）。在使用花生四烯酸或离子载体 A23187 作为刺激物的共孵育实验中，花生四烯酸代谢物净产量的放射免疫测定表明，在血小板存在的情况下，阿司匹林处理的内皮细胞产生的 6-酮-PGF1 α 实际上可能超过单独未抑制的内皮细胞产生的 6-酮-PGF1 α。在功能测定中，在用花生四烯酸或离子载体 A23187 刺激后，在阿司匹林处理的内皮细胞存在的情况下，血小板聚集受到抑制。相反，使用阿司匹林处理的血小板和未抑制的内皮细胞的反向实验未能证明血小板利用内皮内过氧化物通过上述任何方法产生TXA2。因此，这些研究提供了证据，表明可以发生有效的单向转移和利用血小板衍生的内过氧化物来产生内皮 PGI2。这一过程可能有助于放大血管损伤区域附近 PGI2 的生成，并允许在这些部位紧密定位血小板栓塞的形成。
An important determinant of platelet-vessel wall interactions is the local balance of production of endothelial prostacyclin (PGI2) and platelet thromboxane (TX) A2, labile eicosanoids with opposing effects on hemostasis. Disputed evidence suggests that platelet-derived prostaglandin endoperoxide intermediates may be utilized as substrates for vascular PGI2 synthesis. Using several different approaches, we have found that platelets can transfer endoperoxides to cultured endothelial cells for efficient conversion to PGI2, but a reciprocal transfer of endothelial endoperoxides for utilization by platelet thromboxane synthetase does not occur under the same experimental conditions. However, platelets can utilize arachidonic acid released by endothelial cells for lipoxygenase metabolism. We have directly demonstrated the production of [3H]6-keto-PGF1 alpha (the breakdown product of [3H]PGI2) by aspirin-treated endothelial cells in the presence of platelets stimulated with [3H]arachidonic acid. In coincubation experiments using either arachidonate or ionophore A23187 as a stimulus, radioimmunoassay of the net production of arachidonic acid metabolites showed that 6-keto-PGF1 alpha generation by aspirin-treated endothelial cells in the presence of platelets may actually exceed its generation by uninhibited endothelial cells alone. In functional assays, platelet aggregation was inhibited in the presence of aspirin-treated endothelial cells after stimulation with either arachidonate or ionophore A23187. In contrast, the inverse experiments, using aspirin-treated platelets and uninhibited endothelial cells, failed to demonstrate platelet utilization of endothelial endoperoxides for TXA2 production by any of the above methods. These studies thus provide evidence that efficient unidirectional transfer and utilization of platelet-derived endoperoxides for endothelial PGI2 production can occur. This process may serve to amplify PGI2 generation adjacent to areas of vascular injury and permit tight localization of platelet plug formation at these sites.