Cysteinyl leukotriene receptors, old and new; implications for asthma.

Cysteinyl leukotriene receptors, old and new; implications for asthma.
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DOI:
10.1111/j.1365-2222.2012.03982.x
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发表时间:
2012-09
期刊:
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
影响因子:
--
通讯作者:
Boyce JA
Boyce JA
中科院分区:
其他
文献类型:
--
作者:
Laidlaw TM;Boyce JA

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半胱氨酰白三烯(Cys-Lts)是三种结构相似但功能不同的炎症脂质介质。亲本Cys-LT,LTC4,由肥大细胞、嗜酸性粒细胞、嗜碱性粒细胞和巨噬细胞合成和释放,并转化为强大的收缩因子LTD4和稳定的代谢物LTE4。虽然目前只鉴定、克隆和鉴定了两个Cys-LT选择性受体(CysLTRs),但早在三十年前的研究就预测到至少存在三个具有功能的CysLTRs,每个都在呼吸道和其他组织中具有独特的生理功能。最近的证据表明,缺乏这两种已知CysLTRs的小鼠对Cys-LTs表现出完整的(在某些情况下,增强的)生理反应,证实了未知CysLTRs的存在。此外,在整个动物和细胞系统中操纵受体表达的能力表明,CysLTRs的功能受到多个水平的控制,包括受体与受体的相互作用。最后,在转基因小鼠中的研究揭示了Cys-Lts在控制Th2对常见过敏原的诱导反应中的潜在主要作用。这篇综述着重于这些最新的发现及其潜在的临床意义。
The cysteinyl leukotrienes (cys-LTs) are three structurally similar, but functionally distinct lipid mediators of inflammation. The parent cys-LT, LTC4, is synthesized by and released from mast cells, eosinophils, basophils, and macrophages, and is converted to the potent constrictor LTD4 and the stable metabolite, LTE4. While only two cys-LT-selective receptors (CysLTRs) have been identified, cloned, and characterized, studies dating back three decades predicted the existence of at least three functional CysLTRs, each with a characteristic physiological function in airways and other tissues. The recent demonstration that mice lacking both known CysLTRs exhibit full (and in some instances, augmented) physiological responses to cys-LTs verifies the existence of unidentified CysLTRs. Moreover, the ability to manipulate receptor expression in both whole animal and cellular systems reveals that the functions of CysLTRs are controlled at multiple levels, including receptor-receptor interactions. Finally, studies in transgenic mice have uncovered a potentially major role for cys-LTs in controlling the induction of Th2 responses to common allergens. This review focuses on these recent findings and their potential clinical implications.
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