Effects of epoxyeicosatrienoic acids on polymorphonuclear leukocyte function.
Effects of epoxyeicosatrienoic acids on polymorphonuclear leukocyte function.
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DOI：
10.1016/s0024-3205(02)01533-3
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发表时间：
2002-04
期刊：
影响因子：
6.1
通讯作者：
P. Pratt;M. Rosolowsky;W. Campbell
中科院分区：
文献类型：
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作者：
P. Pratt;M. Rosolowsky;W. Campbell
在缺血和血管损伤期间，释放的因子通过促进对内皮的粘附和跨内皮细胞（EC）层的迁移，将单核细胞和多形核白细胞（PMN）募集到损伤部位。在冠状动脉狭窄期间，我们发现内皮衍生的花生四烯酸细胞色素 P450 代谢物环氧二十碳三烯酸 (EET) 升高。因此，我们研究了 EET 是否可以刺激 PMN 粘附到培养的 EC 上。用EET预处理EC 30分钟或4小时并没有改变51 Cr标记的PMN对EC的粘附，而佛波醇肉豆蔻酸酯乙酸酯(PMA)使PMN粘附增加4倍。 EET 和 PMA 的组合并没有显着增强或减弱 PMA 诱导的 PMN 对 EC 的粘附。当 EC 和 51 Cr 标记的 PMN 共孵育时，单独使用 EET 治疗不会改变 PMN 的粘附性。然而，当 EET 和 PMA 在 EC 和 51 Cr 标记的 PMN 共孵育过程中添加在一起时，EET 会导致 PMN 粘附性出现与浓度相关的下降。对浸泡细胞的培养基进行显微镜分析揭示了标记的中性粒细胞的聚集体。我们研究了 EET 对 PMN 聚集的影响。 8,9-EET（10、50 和 100 μM）使 PMN 聚集（7 ± 3、35 ± 10 和 65 ± 11%）和细胞内钙增加至基础值的 1.7 ± 0.5、4.7 ± 1.4 和 6.8 ± 2.3 倍。 5,6-、11,2-和14,15-EET也刺激聚集。 FMLP 刺激超氧化物的产生；然而，8,9-EET 却没有。这些观察结果表明，共孵育实验中观察到的 PMN 粘附性下降是 EET 诱导的 PMN 聚集的结果。鉴于冠状动脉狭窄期间 EET 产生的增加，这些数据可能有助于深入了解它们在心肌缺血和血管损伤期间的潜在生物学意义。
During periods of ischemia and vascular injury, factors are released which recruit monocytes and polymorphonuclear leukocytes (PMNs) to the site of injury by promoting adherence to the endothelium and transmigration across the endothelial cell (EC) layer. During coronary artery stenosis, we have shown that the endothelium-derived, cytochrome P450metabolites of arachidonic acid, the epoxyeicosatrienoic acids (EETs), are elevated. Therefore, we examined if the EETs could stimulate PMN adherence to cultured ECs. Pretreatment of ECs with EETs for either 30 min or 4 hr did not alter the adherence of51Cr-labelled PMNs to ECs while phorbol myristate acetate (PMA) produced a 4-fold increase in PMN adherence. The combination of EETs and PMA did not significantly augment or diminish PMA-induced PMN adherence to ECs. When ECs and51Cr-labelled PMNs were coincubated, treatment with EETs alone did not alter PMN adherence. However, when EETs and PMA were added together during the coincubation of ECs and51Cr-labelled PMNs, the EETs produced a concentration-related decrease in PMN adherence. Microscopic analysis of the culture media bathing the cells revealed aggregates of the labeled PMNs. We examined the effects of the EETs on PMN aggregation. 8,9-EET (10, 50, and 100 μM) increased PMN aggregation (7 ± 3, 35 ± 10, and 65 ± 11%) and intracellular calcium by 1.7 ± 0.5, 4.7 ± 1.4, and 6.8 ± 2.3-fold above basal. 5,6-, 11,2- and 14,15-EETs also stimulated aggregation. FMLP stimulated the production of superoxide; however, 8,9-EET did not. These observations indicate that the decrease in PMN adherence observed in the coincubation experiment is the result of EET-induced PMN aggregation. Given the increase in EET production during coronary artery stenosis, these data may provide insight into their potential biological significance during myocardial ischemia and vascular injury.