12(R)-HYDROXY-5,8,10,14-EICOSATETRAENOIC ACID IS A CHEMOATTRACTANT FOR HUMAN POLYMORPHONUCLEAR LEUKOCYTES INVITRO
12(R)-HYDROXY-5,8,10,14-EICOSATETRAENOIC ACID IS A CHEMOATTRACTANT FOR HUMAN POLYMORPHONUCLEAR LEUKOCYTES INVITRO
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DOI：
10.1016/0090-6980(87)90264-4
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发表时间：
1987-07-01
影响因子：
2.9
通讯作者：
WOOLLARD, PM
中科院分区：
文献类型：
--
作者：
CUNNINGHAM, FM;WOOLLARD, PM
与临床正常皮肤相比，在患有皮肤病银屑病的患者的病变皮肤中发现12-羟基-5，8，10，14-二十碳四烯酸（12-HETE）的量增加。立体化学分析最近表明，在银屑病皮损中存在的12-HETE是由血小板产生的（R），而不是（S）羟基对映体。由于12（R）-HETE的化学引诱物活性以前没有描述过，现在已经合成了12-HETE的（R）和（S）羟基对映体，并在体外比较了它们的化学动力学活性。12（R）-HETE作为人多形核白细胞的化学动力学试剂比12（S）-HETE更有效，但比白三烯B4的效力低2000倍。与用12-HETE对映体获得的结果相反，发现化学引诱化合物5（S）-HETE比5（R）羟基对映体更有效。因此，羟基的构型似乎对HETE的化学动力学活性是重要的，并且12（R）对映体的增加的效力可以增强其作为银屑病中炎症介质的重要性。
Increased amounts of 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) are found in the lesional skin of patients with the skin disease psoriasis when compared to clinically normal skin. Stereochemical analysis has recently shown that the 12-HETE present in lesional psoriatic scale is the (R), and not the (S) hydroxyl enantiomer, produced by platelets. Since the chemoattractant activity of 12(R)-HETE has not previously been described, the (R) and (S) hydroxyl enantiomers of 12-HETE have now been synthesised and their chemokinetic activity compared in vitro. 12(R)-HETE, was more potent than 12(S)-HETE as a chemokinetic agent for human polymorphonuclear leucocytes but 2000 times less potent than leukotriene B4. In contrast to results obtained with the 12-HETE enantiomers, the chemoattractant compound 5(S)-HETE was found to be more potent than the 5(R) hydroxyl enantiomer. Thus, the configuration of the hydroxyl group appears to be of importance to the chemokinetic activity of the HETEs, and the increased potency of the 12(R) enantiomer may enhance its significance as a mediator of inflammation in psoriasis.