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A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis

机译：介导趋化性的白三烯B4的G蛋白偶联受体

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摘要

Leukotriene B4 (LTB4) is a potent chemoattractant that is primarily involved in inflammation, immune responses and host defence against infection. LTB4 activates inflammatory cells by binding to its cell-surface receptor (BLTR). LTB4 can also bind and activate the intranudear transcription factor PPAR alpha, resulting in the activation of genes that terminate inflammatory processes. Here we report the cloning of the complementary DNA encoding a cell-surface LTB4 receptor that is highly expressed in human leukocytes. Using a subtraction strategy, we isolated two cDNA clones (HL-1 and HL-5) from retinoic acid-differentiated HL-60 cells. These two clones contain identical open reading frames encoding a protein of 352 amino acids and predicted to contain seven membrane-spanning domains, but different 5'-untranslated regions. Membrane fractions of Cos-7 cells transfected with an expression construct containing the open reading frame of HL-5 showed specific LTB4 binding, with a K(d) (0.154nM) comparable to that observed in retinoic acid-differentiated HL-60 cells. In CHO cells stably expressing this receptor, LTB4 induced increases in intracellular calcium, D-myo-inositol-1,4,5-triphosphate (InsP3) accumulation, and inhibition of adenylyl cyclase. Furthermore, CHO cells expressing exogenous BLTR showed marked chemotactic responses towards low concentrations of LTB4 in a pertussis-toxin-sensitive manner. Our findings, together with previous reports, show that LTB4 is a unique lipid mediator that interacts with both cell-surface and nuclear receptors.
机译：白三烯B4（LTB4）是一种有效的化学引诱剂，主要参与炎症反应，免疫反应和宿主防御感染。 LTB4通过结合其细胞表面受体（BLTR）激活炎性细胞。 LTB4还可以结合并激活内转录因子PPARα，从而激活终止炎症过程的基因。在这里，我们报告了编码在人白细胞中高度表达的细胞表面LTB4受体的互补DNA的克隆。使用减法策略，我们从视黄酸分化的HL-60细胞中分离了两个cDNA克隆（HL-1和HL-5）。这两个克隆包含编码352个氨基酸的蛋白质的相同开放阅读框，并预计包含七个跨膜结构域，但具有不同的5'非翻译区。用含有HL-5开放阅读框的表达构建体转染的Cos-7细胞膜级分显示特异性LTB4结合，其K（d）（0.154nM）与在视黄酸分化的HL-60细胞中观察到的相当。在稳定表达该受体的CHO细胞中，LTB4诱导细胞内钙，D-肌醇-1,4,5-三磷酸（InsP3）积累和腺苷酸环化酶抑制作用增加。此外，表达外源BLTR的CHO细胞以百日咳毒素敏感的方式对低浓度的LTB4表现出明显的趋化反应。我们的发现以及以前的报道表明，LTB4是一种独特的脂质介体，可与细胞表面和核受体相互作用。

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