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6-反式白三烯B4是豚鼠真皮中的一种中性粒细胞趋化因子。

6-trans-leukotriene B4 is a neutrophil chemotaxin in the guinea pig dermis.

作者信息

Fretland D J, Widomski D L, Anglin C P, Walsh R E, Levin S, Gaginella T S

机构信息

Gastrointestinal Diseases Research, G.D. Searle and Co., Skokie, Illinois 60077.

出版信息

J Leukoc Biol. 1991 Mar;49(3):283-8. doi: 10.1002/jlb.49.3.283.

Abstract

The products of the 5- and 12-lipoxygenase (5-LO, 12-LO) pathways of arachidonic acid metabolism are implicated as proinflammatory mediators in a number of disease states. 12(R)-hydroxyeicosatetraenoic acid [12(R)-HETE] is present in large quantities in human psoriatic lesional skin and can be further metabolized by 5-LO to 5(S), 12(R)-dihydroxy-(6E,8Z,10E,14Z)-eicosatetraenoic acid (6-trans-LTB4). Furthermore, leukotriene B4 (LTB4) and the sulfidopeptide leukotrienes (LTC4, LTD4) can be transformed to 6-trans-LTB4. When injected into the guinea pig dermis, 6-trans-LTB4 (1.0, 10.0, 20.0 micrograms/intradermal site) caused a significant (P less than 0.02) infiltration of polymorphonuclear leukocytes (PMN) at 4 hr as assessed by histology and the levels of the PMN marker enzyme myeloperoxidase. 6-trans-LTB4 is a more potent PMN chemoattractant than 12(R)-HETE in the guinea pig dermis but is far less potent than LTB4. Pharmacological interdiction of leukotriene production or receptor binding should take into account the proinflammatory activity of 6-trans-LTB4.

摘要

花生四烯酸代谢的5-脂氧合酶(5-LO)和12-脂氧合酶(12-LO)途径的产物在许多疾病状态下被认为是促炎介质。12(R)-羟基二十碳四烯酸[12(R)-HETE]大量存在于人类银屑病皮损中,并可被5-LO进一步代谢为5(S),12(R)-二羟基-(6E,8Z,10E,14Z)-二十碳四烯酸(6-反式-LTB4)。此外,白三烯B4(LTB4)和硫肽白三烯(LTC4、LTD4)可转化为6-反式-LTB4。当将6-反式-LTB4(1.0、10.0、20.0微克/皮内注射部位)注入豚鼠真皮时,通过组织学和中性粒细胞标记酶髓过氧化物酶水平评估,在4小时时引起了显著(P<0.02)的多形核白细胞(PMN)浸润。在豚鼠真皮中,6-反式-LTB4是比12(R)-HETE更强效的PMN趋化剂,但远不如LTB4强效。白三烯产生或受体结合的药理学阻断应考虑6-反式-LTB4的促炎活性。

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