Cunningham F M, Woollard P M
Institute of Dermatology, St. Thomas' Hospital, London, England.
Prostaglandins. 1987 Jul;34(1):71-8. doi: 10.1016/0090-6980(87)90264-4.
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.
与临床正常皮肤相比，在银屑病患者的皮损皮肤中发现12-羟基-5,8,10,14-二十碳四烯酸（12-HETE）的含量增加。立体化学分析最近表明，银屑病皮损鳞屑中存在的12-HETE是由血小板产生的（R）型，而非（S）型羟基对映体。由于此前尚未描述12（R）-HETE的趋化活性，现已合成了12-HETE的（R）型和（S）型羟基对映体，并在体外比较了它们的化学动力学活性。作为人多形核白细胞的化学动力学剂，12（R）-HETE比12（S）-HETE更有效，但效力比白三烯B4低2000倍。与12-HETE对映体的结果相反，发现趋化性化合物5（S）-HETE比5（R）型羟基对映体更有效。因此，羟基的构型似乎对HETEs的化学动力学活性很重要，12（R）对映体效力的增加可能会增强其作为银屑病炎症介质的重要性。
