5-Oxo-eicosanoids Are Potent Eosinophil Chemotactic Factors.

5-Oxo-eicosanoids Are Potent Eosinophil Chemotactic Factors.
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5-氧代二十烷酸是有效的嗜酸性粒细胞趋化因子。

DOI:
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发表时间:
1995
影响因子:
4.8
通讯作者:
J. Schröder
J. Schröder
中科院分区:
生物学2区
文献类型:
--
作者:
U. Schwenk;J. Schröder

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人嗜酸性粒细胞经 5-氧代-二十碳四烯酸或 (5S,15S)-二羟基二十碳四烯酸处理后产生有效的嗜酸性粒细胞趋化类二十烷酸,5-氧代-15-羟基-(6E,8Z,11Z,13E)-二十碳四烯酸 (5-oxo-15-HETE)。 5-Oxo-15-HETE 在纳摩尔浓度下诱导人嗜酸性粒细胞 (Eo) 趋化性,其体外功效与血小板激活因子相当。对几种具有不同取代基和/或双键几何结构的结构相关类二十烷酸的 Eo 趋化活性进行比较得出结论,嗜酸性粒细胞趋化和趋化动力学活性的最大效力和功效存在于 5-氧代-(6E,8Z,11Z,14Z)-二十碳四烯酸 (5-oxo-ETE) 中。 C-15 位羟基的存在对于有效的趋化活性来说并不是必需的,而在 C 原子 8 处具有反式而非顺式双键的几何异构体以及酯化的 5-oxo-ETE 通常显示出 5-10 倍的较低效力。 5-氧代-二十烷酸会引起人 Eos 中细胞内 Ca 水平的剂量依赖性短暂升高,但与其他一些 Eo 趋化素相反,它不会诱导脱颗粒。 Ca 动员和 Eo 趋化性的交叉脱敏表明,5-氧代-二十烷酸、5(S)-HETE 和 (5S,15S)-diHETE 的几何异构体彼此交叉失活 Eo 反应,而其他不相关的刺激不会干扰这些脂质,表明 5-氧代-二十烷酸通过单独的受体激活 Eos。
Human eosinophils produce upon treatment with 5-oxo-eicosatetraenoic acid or (5S,15S)-dihydroxyeicosatetraenoic acid a potent eosinophil-chemotactic eicosanoid, 5-oxo-15-hydroxy-(6E,8Z,11Z,13E)-eicosatetraenoic acid (5-oxo-15-HETE). 5-Oxo-15-HETE induces human eosinophil (Eo) chemotaxis at nanomolar concentrations with an efficacy in vitro comparable to that seen for platelet activating factor. Comparison of Eo chemotactic activities of several structurally related eicosanoids with different substituents and/or double bound geometry led to the conclusion that maximal potency and efficacy of eosinophil-chemotactic and chemokinetic activity is present in 5-oxo-(6E,8Z,11Z,14Z)-eicosatetraenoic acid (5-oxo-ETE). The presence of a hydroxyl group at position C-15 is not necessary for potent chemotactic activity, whereas a geometric isomer having trans instead of cis double bond at C-atom 8, as well as esterified 5-oxo-ETE usually show a 5-10-fold lower potency. 5-Oxo-eicosanoids elicit a dose-dependent transient rise of intracellular Ca levels in human Eos, however, in contrast to some other Eo chemotaxins do not induce degranulation. Cross-desensitization of Ca mobilization and Eo chemotaxis revealed that the geometric isomers of 5-oxo-eicosanoids, 5(S)-HETE, and (5S,15S)-diHETE cross-deactivate Eo responses to each other, whereas other, unrelated stimuli did not interfere with these lipids indicating that 5-oxo-eicosanoids activate Eos via a separate receptor.
DOI: 10.1016/s0065-2776(08)60351-x
发表时间: 1986
影响因子: --
作者:
G. Gleich;C. Adolphson
通讯作者: G. Gleich;C. Adolphson
来自人类嗜酸性粒细胞的花生四烯酸 15-脂氧合酶产物。
DOI: --
发表时间: 1982
期刊: The Journal of biological chemistry
影响因子: --
作者:
Turk,J;Maas,RL;Brash,AR;Roberts2nd,LJ;Oates,JA
通讯作者: Oates,JA
DOI: 10.1073/pnas.91.11.5109
发表时间: 1994-05-24
影响因子: 11.1
作者:
CRUIKSHANK, WW;CENTER, DM;KORNFELD, H
通讯作者: KORNFELD, H