Effects of chronic intracutaneous administration of arachidonic acid and its metabolites. Induction of leukocytoclastic vasculitis by leukotriene B4 and 12-hydroxyeicosatetraenoic acid and its prevention by prostaglandin E2.
Effects of chronic intracutaneous administration of arachidonic acid and its metabolites. Induction of leukocytoclastic vasculitis by leukotriene B4 and 12-hydroxyeicosatetraenoic acid and its prevention by prostaglandin E2.
复制标题
花生四烯酸及其代谢物长期皮内给药的影响。
DOI：
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发表时间：
1987
影响因子：
6.5
通讯作者：
G. Burg
中科院分区：
文献类型：
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作者：
T. Ruzicka;G. Burg
尽管花生四烯酸衍生的代谢物在慢性炎症性皮肤病（如牛皮癣和特应性或接触性皮炎）的病理生理中具有假定的作用，但其慢性应用的皮肤效应尚未被调查。因此，我们系统地研究了豚鼠慢性皮内给药花生四烯酸、前列腺素E2 （PGE2）、白三烯B4 （LTB4）和12-羟基二碳四烯酸（12-HETE）的影响，并描述了以前未被认识到的发现，这些发现与过去报道的短期或局部应用这些炎症介质部分不同。白三烯B4和12-HETE导致大量具有白细胞破裂性血管炎特征的组织学改变。这些变化可以通过同时给药PGE2来预防。在表皮中，LTB4和12-HETE引起一定程度的海绵状病变和增生，增加了氚化胸腺嘧啶放射自显像标记指数。花生四烯酸和PGE2单独使用效果不明显。这些数据表明，除了其他炎症性或增殖性皮肤病外，通过脂氧合酶途径形成的花生四烯酸代谢物可能在白细胞破坏性血管炎中发挥主要作用，而pg可能发挥组织保护作用。
Despite the postulated role of arachidonic acid-derived metabolites in the pathophysiology of chronic inflammatory dermatoses such as psoriasis and atopic or contact dermatitis, the cutaneous effects of their chronic application have not yet been investigated. We therefore studied systematically the effects of chronic intracutaneous administration of arachidonic acid, prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and 12-hydroxyeicosatetraenoic acid (12-HETE) in guinea pigs, and describe previously unrecognized findings partly different from those reported in the past for short-term or topical application of these inflammatory mediators. Leukotriene B4 and 12-HETE led to massive histologic changes characteristic of leukocytoclastic vasculitis. These changes could be prevented by concomitant PGE2 administration. In epidermis, LTB4 and 12-HETE caused some spongiosis as well as hyperplasia and increased tritiated thymidine autoradiographic labeling index. Arachidonic acid and PGE2 alone had little effect. These data suggest that in addition to other inflammatory or hyperproliferative dermatoses, arachidonic acid metabolites formed via lipoxygenase pathways could play a major role in leukocytoclastic vasculitis, whereas PGs could exert a tissue-protective effect.