Production of platelet-activating factor by human vascular endothelial cells: evidence for a requirement for specific agonists and modulation by prostacyclin.
Production of platelet-activating factor by human vascular endothelial cells: evidence for a requirement for specific agonists and modulation by prostacyclin.
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人血管内皮细胞产生血小板激活因子：需要特定激动剂和前列环素调节的证据。
DOI：
10.1161/01.cir.72.4.718
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发表时间：
1985
期刊：
影响因子：
37.8
通讯作者：
S. Prescott
中科院分区：
文献类型：
--
作者：
G. Zimmerman;T. McIntyre;S. Prescott
当用适当的激动剂刺激时，源自人脐静脉的融合内皮细胞的原代培养物会产生血小板活化因子（PAF）（1-烷基-2-乙酰基-SN-甘油-3-磷酸胆碱）。高度纯化的人凝血酶和钙离子载体A23187刺激[3 H]乙酸盐掺入脂质产物中，通过其在薄层色谱和高效液相色谱系统中的行为、特征性生物活性的存在以及对磷脂酶的适当响应，已将其鉴定为PAF。许多其他体液介质因直接影响血管细胞的活性或可能介导内皮损伤而受到检查，但它们不会刺激内皮细胞产生PAF。这表明培养的人内皮细胞合成PAF是对特异性激动剂的反应，而不是由于非特异性细胞扰动而发生的不受调节的事件。凝血酶处理的内皮细胞产生的PAF是血小板活化的有效刺激物，如通过自体血浆中人血小板的聚集所测定的。内皮细胞单层产生的PAF被前列环素（另一种刺激内皮细胞的产物）减弱。相反，PAF的产生是通过用吲哚美辛（花生四烯酸合成前列环素的抑制剂）处理内皮细胞来增强的，这表明内源性产生的前列环素可以调节PAF的合成。PAF是一种独特的脂质autocoid，可刺激血小板和多形核白细胞的活化，其合成的潜力表明内皮细胞可直接影响这些循环效应细胞的活性。这种生物学潜力可能对于生理条件下和血管损伤综合征中内皮与循环血细胞的相互作用很重要。
Primary cultures of confluent endothelial cells derived from human umbilical veins produce platelet-activating factor (PAF) (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) when stimulated with appropriate agonists. Highly purified human thrombin and calcium ionophore A23187 stimulate the incorporation of [3H] acetate into a lipid product that has been identified as PAF by its behavior in thin-layer chromatographic and high-performance liquid chromatographic systems, the presence of characteristic biologic activity, and appropriate response to phospholipases. A number of other humoral mediators, examined because they directly influence the activity of vascular cells or because they may mediate endothelial injury, do not stimulate PAF production by endothelial cells. This indicates that the synthesis of PAF by cultured human endothelial cells is a response to specific agonists and is not an unregulated event that occurs as a result of nonspecific cellular perturbation. The PAF produced by thrombin-treated endothelial cells is a potent stimulus for platelet activation, as assayed by the aggregation of human platelets in autologous plasma. The production of PAF by endothelial monolayers is attenuated by prostacyclin, another product of stimulated endothelial cells. Conversely, PAF production is enhanced by treatment of the endothelial cells with indomethacin, an inhibitor of prostacyclin synthesis from arachidonic acid, indicating that endogenously generated prostacyclin may modulate PAF synthesis. The potential to synthesize PAF, a unique lipid autocoid that stimulates the activation of both platelets and polymorphonuclear leukocytes, suggests that endothelial cells can directly influence the activity of these circulating effector cells. This biologic potential may be important in the interaction of the endothelium with circulating blood cells in physiologic conditions and in syndromes of vascular injury.
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DOI：
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发表时间：
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期刊：
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