Department of Otorhinolaryngology and Head and Neck Surgery, Akita University Graduate School of Medicine, Akita, Japan.
Department of Otorhinolaryngology and Head and Neck Surgery, Akita University Graduate School of Medicine, Akita, Japan.
Allergol Int. 2016 Jul;65(3):280-5. doi: 10.1016/j.alit.2016.01.001. Epub 2016 Feb 10.
The chemokine receptor, CC-chemokine receptor 3 (CCR3), and its major ligands, eotaxin, RANTES, and MCP-4, are involved in eosinophil chemotaxis. It is thought that CCR3 plays an important role in the recruitment and activation of eosinophils in nasal polyposis. We examined nasal polyp extract-induced eosinophil chemotaxis and the effect of a CCR3 antagonist using EZ-TAXIScan, a novel real-time chemotaxis assay device.
Nasal polyps were obtained from chronic rhinosinusitis (CRS) patients during surgery. The polyps were homogenized and eotaxin levels in the extracts were measured. Eosinophils were purified from human peripheral blood by the CD16 negative selection method. Nasal polyp extract-induced eosinophil chemotaxis, with or without CCR3 antagonist, was assessed by EZ-TAXIScan.
There was a significant positive correlation between the eosinophil counts in nasal polyp and eotaxin levels in the nasal polyp extracts. Using EZ-TAXIScan, eosinophil chemotactic responses were observed following stimulation with nasal polyp extracts. There was a significant positive correlation between the chemotactic index toward the nasal polyp extracts and their eotaxin levels. Nasal polyp extract-induced chemotaxis was completely inhibited by CCR3 antagonist but not by chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonist which inhibited PGD2-induced eosinophil chemotaxis.
The CCR3 pathway may play an important role in the pathogenesis of eosinophil recruitment in nasal polyps through selective eosinophil chemotaxis.
趋化因子受体 CC-趋化因子受体 3（CCR3）及其主要配体，嗜酸性粒细胞趋化因子、RANTES 和 MCP-4，参与嗜酸性粒细胞趋化作用。人们认为 CCR3 在鼻息肉中嗜酸性粒细胞的募集和激活中发挥重要作用。我们使用新型实时趋化作用分析设备 EZ-TAXIScan，检测了鼻息肉提取物诱导的嗜酸性粒细胞趋化作用和 CCR3 拮抗剂的作用。
在手术期间从慢性鼻-鼻窦炎（CRS）患者中获取鼻息肉。将息肉匀浆并测量提取物中的嗜酸性粒细胞趋化因子水平。通过 CD16 阴性选择法从人外周血中纯化嗜酸性粒细胞。通过 EZ-TAXIScan 评估有或无 CCR3 拮抗剂时鼻息肉提取物诱导的嗜酸性粒细胞趋化作用。
鼻息肉中的嗜酸性粒细胞计数与鼻息肉提取物中的嗜酸性粒细胞趋化因子水平之间存在显著正相关。使用 EZ-TAXIScan，观察到鼻息肉提取物刺激后嗜酸性粒细胞的趋化反应。趋化指数与鼻息肉提取物的趋化因子水平之间存在显著正相关。CCR3 拮抗剂完全抑制鼻息肉提取物诱导的趋化作用，但对抑制 PGD2 诱导的嗜酸性粒细胞趋化作用的嗜碱性粒细胞趋化因子受体同源分子（CRTH2）拮抗剂没有抑制作用。
CCR3 途径可能通过选择性嗜酸性粒细胞趋化作用在鼻息肉中嗜酸性粒细胞募集的发病机制中发挥重要作用。
