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Critical role of CCL4 in eosinophil recruitment into the airway

机译：CCL4在嗜酸性粒细胞招募到气道的关键作用

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Summary Background Excessive eosinophil airway infiltration is a clinically critical condition in some cases. Eosinophilic pneumonia (EP) is a pulmonary condition involving eosinophil infiltration of the lungs. Although several chemokines, including eotaxin‐1 (CCL11), RANTES (CCL5) and macrophage inflammatory protein 1β (MIP‐1β or CCL4), have been detected in bronchoalveolar lavage fluid (BALF) from patients with EP, the pathophysiological mechanisms underlying EP, including potential relationships between eosinophils and CCL4, have not been fully elucidated. Objective To examine the involvement of CCL4 in eosinophilic airway inflammation. Methods We analysed supernatants of activated eosinophils and BALF from 16 patients with eosinophilic pneumonia (EP). Further, we examined the effects of CCL4 on eosinophil functions in vitro and those of anti‐CCL4 neutralizing antibody in an in vivo model. Results We found that purified human eosinophils stimulated with IL‐5 predominantly secreted CCL4 and that patients with EP had elevated CCL11 and CCL4 levels in BALF compared with samples from individuals without EP. Because CCL4 levels were more strongly correlated with eosinophil count and expression of eosinophil granule proteins than CCL11, in vitro experiments using purified eosinophils concentrated on the former chemokine. Interestingly, CCL4 acted as a chemoattractant for eosinophils. In a mouse model, administration of a CCL4‐neutralizing antibody attenuated eosinophilic airway infiltration and airway hyperresponsiveness. Conclusions and Clinical Relevance Overall, these findings highlight an important role of CCL4 in the mechanisms underlying eosinophil recruitment into the airway and may provide a novel insight into this potential therapeutic target.
机译：发明内容背景嗜酸性粒细胞气道渗透是在某些情况下临床关键状态。嗜酸性肺炎（EP）是一种涉及嗜酸性粒细胞浸润的肺病。虽然几种趋化因子，包括eotaxin-1（CCl11），Rantes（CCl5）和巨噬细胞炎症蛋白1β（MIP-1β或CCl4），但在来自EP患者的支气管肺泡灌洗液（BALF）中，底层底层的病理生理机制，包括嗜酸性粒细胞和CCL4之间的潜在关系，尚未完全阐明。目的探讨CCL4在嗜酸性嗜酸性气道炎症中的参与。方法从嗜酸性肺炎患者（EP）分析了16例活性嗜酸性粒细胞和BALF的上清液。此外，我们研究了CCL4对体内模型中的体外嗜酸性粒细胞功能的影响和体内模型中的抗CCL4中和抗体。结果我们发现用IL-5刺激的纯化的人嗜酸性粒细胞主要分泌的CCL4以及EP患者在BALF中升高了CCL11和CCL4水平，而没有EP的个体的样品。因为CCL4水平与嗜酸性粒细胞计数和嗜酸性粒细胞颗粒蛋白的表达比CCL11更强烈地相关，所以使用浓缩在前趋化因子上的纯化的嗜酸性粒细胞的体外实验。有趣的是，CCL4充当嗜酸性粒细胞的化学术。在小鼠模型中，施用CCL4中和抗体减弱的嗜酸性嗜酸性气道渗透和气道高反应性。结论和临床关联总体而言，这些发现突出了CCL4在嗜酸性粒细胞招募到气道的机制中的重要作用，并可对该潜在的治疗目标提供了一种新的洞察力。

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  • 作者

    Kobayashi Yoshiki; Konno Yasunori; Kanda Akira; Yamada Yoshiyuki; Yasuba Hirotaka; Sakata Yoshiko; Fukuchi Mineyo; Tomoda Koichi; Iwai Hiroshi; Ueki Shigeharu;

  • 作者单位

    Airway Disease Section Department of OtolaryngologyKansai Medical UniversityOsaka Japan;

    Department of General Medical Practice and Laboratory Diagnostic MedicineAkita University Graduate;

    Airway Disease Section Department of OtolaryngologyKansai Medical UniversityOsaka Japan;

    Department of Allergy and ImmunologyGunma Children’s Medical CenterGunma Japan;

    Department of Airway MedicineMitsubishi Kyoto HospitalKyoto Japan;

    Central Research of LaboratoryKansai Medical UniversityOsaka Japan;

    Department of General Medical Practice and Laboratory Diagnostic MedicineAkita University Graduate;

    Airway Disease Section Department of OtolaryngologyKansai Medical UniversityOsaka Japan;

    Airway Disease Section Department of OtolaryngologyKansai Medical UniversityOsaka Japan;

    Department of General Medical Practice and Laboratory Diagnostic MedicineAkita University Graduate;

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  • 正文语种 eng
  • 中图分类 医学免疫学;
  • 关键词

    chemokines; clinical immunology; eosinophils;

    机译：趋化因子;临床免疫学;嗜酸性粒细胞;

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