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首页> 外文期刊>American Journal of Physiology >The UDP-sugar-sensing P2Y 14 receptor promotes Rho-mediated signaling and chemotaxis in human neutrophils
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The UDP-sugar-sensing P2Y 14 receptor promotes Rho-mediated signaling and chemotaxis in human neutrophils

机译：UDP糖敏感的P2Y 14受体在人类嗜中性粒细胞中促进Rho介导的信号传导和趋化性

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摘要

The G i-coupled P2Y 14 receptor (P2Y 14-R) is potently activated by UDP-sugars and UDP. Although P2Y 14-R mRNA is prominently expressed in circulating neutrophils, the signaling pathways and functional responses associated with this receptor are undefined. In this study, we illustrate that incubation of isolated human neutrophils with UDPglucose resulted in cytoskeleton rearrangement, change of cell shape, and enhanced cell migration. We also demonstrate that UDP-glucose promotes rapid, robust, and concentration-dependent activation of RhoA in these cells. Ecto-nucleotidases expressed on neutrophils rapidly hydrolyzed extracellular ATP, but incubation with UDPglucose for up to 1 h resulted in negligible metabolism of the nucleotide-sugar. HL60 human promyelocytic leukemia cells do not express the P2Y 14-R, but neutrophil differentiation of HL60 cells with DMSO resulted in markedly enhanced P2Y 14-R expression. Accordingly, UDP-glucose, UDP-galactose, and UDP-N-acetylglucosamine promoted Rho activation in differentiated but not in undifferentiated HL60 cells. Stable expression of recombinant human P2Y14-R conferred UDP-sugar-promoted responses to undifferentiated HL60 cells. UDP-glucose-promoted RhoA activation also was accompanied by enhanced cell migration in differentiated HL60 cells, and these responses were blocked by Rho kinase inhibitors. These results support the notion that UDP-glucose is a stable and potent proinflammatory mediator that promotes P2Y 14-R-mediated neutrophil motility via Rho/Rho kinase activation.
机译：G i偶联的P2Y 14受体（P2Y 14-R）被UDP糖和UDP有效激活。尽管P2Y 14-R mRNA在循环中性粒细胞中显着表达，但与该受体相关的信号传导途径和功能反应尚不确定。在这项研究中，我们说明了用UDP葡萄糖孵育分离的人类嗜中性粒细胞会导致细胞骨架重排，细胞形状改变和增强的细胞迁移。我们还证明了UDP葡萄糖可以促进这些细胞中RhoA的快速，稳定和浓度依赖性激活。在嗜中性粒细胞上表达的顺式核苷酸酶迅速水解细胞外ATP，但与UDP葡萄糖温育长达1小时导致核苷酸糖的代谢可忽略不计。 HL60人早幼粒细胞白血病细胞不表达P2Y 14-R，但是用DMSO对HL60细胞的中性粒细胞分化导致P2Y 14-R表达明显增强。因此，UDP-葡萄糖，UDP-半乳糖和UDP-N-乙酰氨基葡糖在分化的而非未分化的HL60细胞中促进Rho活化。重组人P2Y14-R的稳定表达赋予UDP糖促进的未分化HL60细胞应答。 UDP葡萄糖促进的RhoA激活还伴随着分化的HL60细胞中细胞迁移的增强，并且这些反应被Rho激酶抑制剂阻断。这些结果支持以下观点：UDP葡萄糖是一种稳定且有效的促炎介质，可通过Rho / Rho激酶激活来促进P2Y 14-R介导的嗜中性粒细胞运动。

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