Endothelial cell leukotriene C4 synthesis results from intercellular transfer of leukotriene A4 synthesized by polymorphonuclear leukocytes.
Endothelial cell leukotriene C4 synthesis results from intercellular transfer of leukotriene A4 synthesized by polymorphonuclear leukocytes.
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DOI：
10.1016/s0021-9258(18)66589-5
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发表时间：
1986-12
期刊：
影响因子：
--
通讯作者：
S. Feinmark;P. Cannon
中科院分区：
文献类型：
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作者：
S. Feinmark;P. Cannon
本文研究了猪主动脉内皮细胞合成和代谢白三烯的情况。通过豚鼠肺实质条生物测定法、放射免疫测定法和紫外分光光度法与高效液相色谱法的组合来鉴定白三烯。用钙离子载体A23187刺激的内皮细胞不能将花生四烯酸转化为可检测水平的LTA 4衍生产物，包括生物活性代谢物LTB 4或LTC 4。然而，这些细胞很容易将外源LTA 4转化为有效的慢反应物质LTC 4。还观察到较少量的11-trans-LTC 4和LTD 4。在这些孵育中未检测到LTB 4，也未观察到LTB 4代谢。由于多形核白细胞（PMNL）受刺激时可释放LTA 4，并与内皮细胞有明显的接触，因此LTA 4可能在PMNL和内皮细胞之间转移。当A23187刺激的中性粒细胞与内皮细胞共孵育时，在单独的PMNL上检测到LTC 4水平的显著增加。LTC 4由谷胱甘肽（GSH）与LTA 4的酶促缀合形成。因此，在一些实验中，用[35 S]半胱氨酸预标记内皮细胞以允许[35 S]GSH的细胞内合成。当未标记的PMNL作为LTA 4的来源加入到预标记的内皮细胞中时，回收了大量的[35 S] LTC 4。数据表明，内皮细胞从LTA 4合成LTC 4。他们还证明了一个特定的PMNL-内皮细胞的相互作用，其中内皮细胞LTC 4的合成结果从细胞间转移的LTA 4产生的PMNL。
Leukotriene (LT) synthesis and metabolism were studied in porcine aortic endothelial cells. Leukotrienes were identified by combinations of guinea pig lung parenchymal strip bioassay, radioimmunoassay, and UV spectrophotometry with high performance liquid chromatography. Endothelial cells stimulated with the calcium ionophore, A23187, were unable to convert arachidonic acid to detectable levels of LTA4-derived products including the biologically active metabolites, LTB4 or LTC4. However, these cells readily converted exogenous LTA4 to the potent slow-reacting substance, LTC4. Smaller quantities of 11-trans-LTC4 and LTD4 were also observed. LTB4 was not detectable in these incubations nor was LTB4 metabolism observed. The possible intercellular transfer of LTA4 between polymorphonuclear leukocytes (PMNL) and endothelial cells was tested since PMNL release LTA4 when stimulated and have significant contact with endothelium. When A23187-stimulated neutrophils were coincubated with endothelial cells, a significant increase in LTC4 levels was detected over PMNL alone. LTC4 is formed by the enzymatic conjugation of glutathione (GSH) with LTA4. Therefore in some experiments, endothelial cells were prelabeled with [35S]cysteine to allow intracellular synthesis of [35S]GSH. When unlabeled PMNL were added, as a source of LTA4 to the prelabeled endothelial cells, substantial levels of [35S] LTC4 were recovered. The data indicate that endothelial cells synthesize LTC4 from LTA4. They also demonstrate a specific PMNL-endothelial cell interaction in which endothelial cell LTC4 synthesis results from the intercellular transfer of LTA4 produced by PMNL.