PDF(Pubmed)
Abstract：
Atypical chemokine receptor-1 (ACKR1), previously known as the Duffy antigen receptor for chemokines, is a widely conserved cell surface protein that is expressed on erythrocytes and the endothelium of post-capillary venules. In addition to being the receptor for the parasite causing malaria, ACKR1 has been postulated to regulate innate immunity by displaying and trafficking chemokines. Intriguingly, a common mutation in its promoter leads to loss of the erythrocyte protein but leaves endothelial expression unaffected. Study of endothelial ACKR1 has been limited by the rapid down-regulation of both transcript and protein when endothelial cells are extracted and cultured from tissue. Thus, to date the study of endothelial ACKR1 has been limited to heterologous over-expression models or the use of transgenic mice. Here we report that exposure to whole blood induces ACKR1 mRNA and protein expression in cultured primary human lung microvascular endothelial cells. We found that contact with neutrophils is required for this effect. We show that NF-κB regulates ACKR1 expression and that upon removal of blood, the protein is rapidly secreted by extracellular vesicles. Finally, we confirm that endogenous ACKR1 does not signal upon stimulation with IL-8 or CXCL1. Our observations define a simple method for inducing endogenous endothelial ACKR1 protein that will facilitate further functional studies.
摘要：
非典型趋化因子受体-1（ACKR1），以前被称为趋化因子的达菲抗原受体，是一种广泛保守的细胞表面蛋白，在红细胞和毛细血管后小静脉的内皮上表达。除了是引起疟疾的寄生虫的受体，已经假定ACKR1通过展示和运输趋化因子来调节先天免疫。有趣的是，其启动子中的一个常见突变导致红细胞蛋白的丢失，但不影响内皮表达。当从组织中提取和培养内皮细胞时，转录物和蛋白质的快速下调限制了对内皮ACKR1的研究。因此，迄今为止,内皮ACKR1的研究仅限于异源过表达模型或使用转基因小鼠。在这里，我们报告了暴露于全血可诱导培养的原代人肺微血管内皮细胞中ACKR1mRNA和蛋白质表达。我们发现，这种作用需要与中性粒细胞接触。我们表明NF-κB调节ACKR1的表达，并且在去除血液时，该蛋白由细胞外囊泡迅速分泌。最后,我们证实内源性ACKR1在用IL-8或CXCL1刺激后不发出信号。我们的观察结果确定了诱导内源性内皮ACKR1蛋白的简单方法，这将有助于进一步的功能研究。
