Background

Our previous studies revealed the presence of interleukin-5 (IL-5) receptor alpha chain (IL-5Rα, CD125) on neutrophils in a murine model of influenza and in the lung fluid of children with severe asthma.

Objective

To further evaluate the functional characteristics and effects of clinical factors and inflammatory variables on neutrophil surface IL-5Rα abundance in lung fluid and blood.

Methods

IL-5Rα expression was quantified by flow cytometry performed on purified neutrophils from blood and bronchoalveolar lavage fluid samples obtained from healthy controls and individuals with asthma. Expression was further confirmed by immunohistochemistry. Functional signaling through the IL-5Rα was evaluated by measurement of IL-5–inducible modulation of neutrophil surface CD62L and IL-5Rα expression.

Results

IL-5Rα was consistently present but at a variable magnitude on blood and lung neutrophils. Expression on lung neutrophils was significantly higher than that on blood cells (p"?>P < .001) where their expression was higher in the presence of airway pathogens, especially with respiratory viruses. Increased receptor expression occurred in response to the translocation of preformed receptors from intracellular stores. Receptors were functional as revealed by IL-5–mediated down-regulation of CD62L and the feed-forward up-regulation of reception expression.

Conclusion

In addition to the expression on eosinophils and basophils, the IL-5Rα is consistently and abundantly expressed on the surface of blood and especially air space neutrophils. These observations support the concept that some of the efficacy of IL-5/IL-5R–targeting biologics observed in asthma may reflect their ability to target neutrophilic air space inflammation.

中文翻译：

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白细胞介素 5 受体 α (CD125) 在人血液和肺中性粒细胞中的表达

背景

我们之前的研究揭示了流感小鼠模型中的中性粒细胞和严重哮喘儿童的肺液中存在白介素 5 (IL-5) 受体 α 链（IL-5Rα、CD125）。

客观的

进一步评估临床因素和炎症变量对肺液和血液中中性粒细胞表面 IL-5Rα 丰度的功能特征和影响。

方法

通过流式细胞术对从健康对照和哮喘个体获得的血液和支气管肺泡灌洗液样品中纯化的中性粒细胞进行 IL-5Rα 表达定量。通过免疫组织化学进一步证实表达。通过测量 IL-5 诱导的中性粒细胞表面 CD62L 和 IL-5Rα 表达的调节来评估通过 IL-5Rα 的功能信号传导。

结果

IL-5Rα 在血液和肺中性粒细胞中始终存在，但含量不同。肺中性粒细胞上的表达显着高于血细胞上的表达 (p"?> P < .001)，在存在气道病原体（尤其是呼吸道病毒）的情况下，它们的表达更高。受体表达增加是对预先形成的易位的反应。 IL-5 介导的 CD62L 下调和接收表达的前馈上调揭示了受体的功能。

结论

除了在嗜酸性粒细胞和嗜碱性粒细胞上表达外，IL-5Rα 在血液表面、尤其是气腔中性粒细胞表面也持续大量表达。这些观察结果支持这样一个概念，即在哮喘中观察到的 IL-5/IL-5R 靶向生物制剂的一些功效可能反映了它们针对中性粒细胞气腔炎症的能力。