15(S)-HYDROXYEICOSATETRAENOIC ACID IS THE MAJOR ARACHIDONIC-ACID METABOLITE IN HUMAN BRONCHI - ASSOCIATION WITH AIRWAY EPITHELIUM
15(S)-HYDROXYEICOSATETRAENOIC ACID IS THE MAJOR ARACHIDONIC-ACID METABOLITE IN HUMAN BRONCHI - ASSOCIATION WITH AIRWAY EPITHELIUM
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DOI：
10.1016/0003-9861(90)90114-e
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发表时间：
1990-11-01
影响因子：
3.9
通讯作者：
DAHLEN, SE
中科院分区：
文献类型：
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作者：
KUMLIN, M;HAMBERG, M;DAHLEN, SE
15(S)-羟基-5，8，11，13-二十碳四烯酸(15-HETE)经反相高效液相色谱、紫外光谱、气相色谱-质谱法(GC/MS)鉴定为花生四烯酸在人支气管中含量最高的代谢物。以16(S)-hydroxy-9(Z)，12(Z)，14(E)-heneicosatrienoic酸为内标进行了单羟基二十碳四烯酸(Mono-HETE)的定量。因此，单独在缓冲液中孵育支气管可获得显著数量的15-HETE，但外源花生四烯酸(3-100微米)可剂量依赖性地增加这种形成，最大水平在10分钟左右达到。相反，用离子载体A23187或抗人IgE激发并不刺激15-HETE在支气管中的产生。去甲二氢愈创木酸抑制15-HETE的产生，而吲哚美辛则不抑制。在外源15H(P)ETE的孵育中检测到少量的8，15-diHETE。然而，在所使用的任何孵育条件下都没有检测到脂氧素。此外，去除呼吸道上皮实质上减少了15-HETE在支气管中的产生。最后，取自三名哮喘患者的支气管，这些标本中15-HETE的含量显著高于非哮喘患者的组织中的含量。在外周肺实质和肺血管中，花生四烯酸刺激后15-HETE是主要的单HETE，但水平比支气管低约10倍。另一个区别是，用离子载体A23187挑战薄壁组织，使5-HETE成为主要的单HETE。综上所述，呼吸道上皮细胞似乎是人类肺中15-HETE的主要来源，在哮喘患者标本中的发现增加了15-HETE以某种方式参与呼吸道炎症的可能性。
15(S)-Hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) was by far the most abundant metabolite of arachidonic acid in chopped human bronchi, as identified by reverse phase HPLC, uv spectrometry, and GC/MS. The quantitation of monohydroxyeicosatetraenoic acids (mono-HETEs) was performed by the use of 16(S)-hydroxy-9(Z),12(Z),14(E)-heneicosatrienoic acid as internal standard. Thus, significant amounts of 15-HETE were obtained in incubations of bronchi in buffer alone, but the addition of exogenous arachidonic acid (3-100 .mu.M), dose-dependently increased the formation, with maximal levels reached at around 10 min. In contrast, challenge with ionophore A23187 or anti-human IgE did not stimulate the production of 15-HETE in the bronchi. Nordihydroguaiaretic acid inhibited the production of 15-HETE, whereas indomethacin did not. Small amounts of 8,15-diHETEs were detected in incubations with exogenous 15H(P)ETE. Lipoxins were however not detected under any of the incubation conditions used. Furthermore, removal of the airway epithelium substantially diminished the production of 15-HETE in the bronchi. Finally, bronchi were obtained from three patients with asthma, and the amounts of 15-HETE in these specimens were significantly higher than those found in tissues from nonasthmatics. Also, in peripheral lung parenchyma and pulmonary blood vessels 15-HETE was the major mono-HETE after stimulation with arachidonic acid but the levels were about 10 times lower than in the bronchi. As another difference, challenge of the parenchyma with the ionophore A23187 made 5-HETE the predominant mono-HETE. Taken together, airway epithelium appears to be the major source of 15-HETE in the human lung and the findings in specimens of asthmatics raise the possibility that 15-HETE somehow is involved in airway inflammation.