PEPTIDO-LEUKOTRIENES ARE POTENT AGONISTS OF VON-WILLEBRAND-FACTOR SECRETION AND P-SELECTIN SURFACE EXPRESSION IN HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS
PEPTIDO-LEUKOTRIENES ARE POTENT AGONISTS OF VON-WILLEBRAND-FACTOR SECRETION AND P-SELECTIN SURFACE EXPRESSION IN HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS
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DOI：
10.1161/01.cir.92.11.3304
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发表时间：
1995-12-01
期刊：
影响因子：
37.8
通讯作者：
EWENSTEIN, BM
中科院分区：
文献类型：
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作者：
DATTA, YH;ROMANO, M;EWENSTEIN, BM
肽白三烯（LTs）和脂毒素（LX）是血小板在血管炎症和损伤部位（如冠状动脉球囊血管成形术）通过白细胞来源的LTA(4)的跨细胞转化产生的。我们研究了这些类二十烷类化合物对血管内皮的作用。方法和结果我们发现，用LTC(4)和LTD(4)刺激培养的人脐静脉内皮细胞（EC），可导致血管性血液病因子（vWF）的高分子量多聚体以浓度和时间依赖性的方式释放，通过ELISA检测。LXA(4)和LXB(4)均未刺激vWF释放。LTC(4)和LTD(4)也刺激了p -选择素表面表达的快速增加，这表明抗p -选择素单克隆抗体包被珠的结合增加。荧光细胞术检测到EC中[Ca2+](i)的延长峰，以响应凝血酶和LTD(4)的浓度，诱导vWF分泌接近最大。相比之下，在大多数EC中，诱导相似水平vWF分泌的LTC(4)浓度只产生[Ca2+]的异步振荡(i)，很少诱导[Ca2+]的延长峰值(i)。外部Ca2+的消耗对lt刺激的[Ca2+](i)瞬态和vWF分泌没有明显影响，暗示细胞内池是这种反应的来源。Staurosporine，鞘氨醇和H-7对肽- lt诱导的vWF分泌只有适度的影响，这表明蛋白激酶C不是肽- lt诱导的胞吐的主要介质。环氧化酶和血小板活化因子抑制剂对肽- lt介导的VWF分泌无影响。结论肽- lts通过诱导vWF分泌和p -选择素表面表达，可能在止血和炎症的相关过程中发挥重要作用。
Background The peptido-leukotrienes (LTs) and lipoxins (LX) are produced by platelets through the transcellular conversion of leukocyte-derived LTA(4) at sites of vascular inflammation and injury, such as during coronary artery balloon angioplasty. We studied the actions of these eicosanoids on vascular endothelium.Methods and Results We found that stimulation of cultured human umbilical vein endothelial cells (EC) with LTC(4) and LTD(4) resulted in the release of high-molecular-weight multimers of von Willebrand factor (vWF) in a concentration- and time-dependent fashion, as measured by ELISA. Neither LXA(4) nor LXB(4) stimulated vWF release. LTC(4) and LTD(4) also stimulated a rapid increase in the surface expression of P-selectin indicated by increased binding of anti-P-selectin monoclonal antibody-coated beads. Fluorescence cytometry detected prolonged peaks of [Ca2+](i) in EC in response to concentrations of thrombin and LTD(4) that induce near-maximal vWF secretion. In contrast, concentrations of LTC(4) that induce similar levels of vWF secretion produced only asynchronous oscillations of [Ca2+](i) in most EC and rarely induced prolonged peaks of [Ca2+](i). Depletion of external Ca2+ had no apparent impact on LT-stimulated [Ca2+](i) transients and vWF secretion, implicating an intracellular pool as the source of this response. Staurosporine, sphingosine, and H-7 each had only modest effects on peptido-LT-induced vWF secretion, suggesting that protein kinase C is not a primary mediator of peptide-LT-induced exocytosis. Inhibitors of cyclooxygenase and platelet-activating factor had no effect on peptido-LT-mediated VWF secretion.Conclusions Through the induction of vWF secretion and P-selectin surface expression, peptido-LTs are likely to play an important role in the interrelated processes of hemostasis and inflammation.