Background

Myeloid cells, especially dendritic cells and macrophages, play important roles in asthma pathophysiology. Monocytes (Mo) and macrophages express protease-activated receptor-2 (PAR-2), a proinflammatory serine protease receptor implicated in the pathophysiology of allergic airway inflammation. We have revealed that patients with severe asthma and those with a history of frequent asthma exacerbations exhibit increased PAR-2 expression on peripheral blood monocytes.

Objective

To determine PAR-2 expression on peripheral blood intermediate monocytes (IMMo) in subjects with increased airway inflammation, either as a result of an asthma exacerbation or after an inhalation allergen challenge.

Methods

A total of 16 adults who presented to the emergency department with asthma exacerbations were recruited after giving an informed consent. After 2 weeks, 10 patients returned for follow-up. A total of 11 patients with mild asthma treated only with as-needed bronchodilators were recruited and underwent inhalation allergen challenge after providing an informed consent. Immune cell profiling was performed by whole blood flow cytometry in both groups of patients.

Results

PAR-2 expression in peripheral blood IMMo increased in patients with an asthma exacerbation compared with those with stable disease, but this expression decreased after treatment of the asthma exacerbation. Subjects with mild asthma had an increase in percentages of IMMo expressing PAR-2 after an allergen challenge. Patients who presented to the emergency department had lower dendritic cell and dendritic cell subset numbers in peripheral blood during exacerbation compared with after treatment.

Conclusion

Increased PAR-2 expression on Mo during periods of increased airway inflammation may initiate a positive feedback loop leading to systemic inflammatory changes.

中文翻译：

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外周血中间体单核细胞蛋白酶激活受体 2 表达在哮喘发作期间和吸入过敏原攻击后增加

背景

骨髓细胞，尤其是树突状细胞和巨噬细胞，在哮喘病理生理学中起重要作用。单核细胞 (Mo) 和巨噬细胞表达蛋白酶激活受体 2 (PAR-2)，这是一种促炎丝氨酸蛋白酶受体，与过敏性气道炎症的病理生理学有关。我们发现重度哮喘患者和有频繁哮喘发作史的患者外周血单核细胞上的 PAR-2 表达增加。

客观的

确定气道炎症增加的受试者外周血中间单核细胞 (IMMo) 上的 PAR-2 表达，无论是由于哮喘恶化还是在吸入过敏原激发后。

方法

在获得知情同意后，共招募了 16 名因哮喘发作而就诊于急诊科的成年人。2 周后，10 名患者返回进行随访。总共招募了 11 名仅使用按需支气管扩张剂治疗的轻度哮喘患者，并在提供知情同意后接受了吸入过敏原激发。通过全血流式细胞术对两组患者进行免疫细胞分析。

结果

与病情稳定的患者相比，哮喘加重患者外周血 IMMo 中 PAR-2 的表达增加，但在哮喘加重治疗后该表达下降。患有轻度哮喘的受试者在过敏原激发后表达 PAR-2 的 IMMo 的百分比增加。与治疗后相比，就诊于急诊科的患者在恶化期间外周血中的树突细胞和树突细胞亚群数量较低。

结论

在气道炎症增加期间，Mo 上 PAR-2 表达的增加可能启动正反馈回路，导致全身炎症变化。