Altered Sphingolipid Metabolism Is Associated With Asthma Phenotype in House Dust Mite-Allergic Patients
Altered Sphingolipid Metabolism Is Associated With Asthma Phenotype in House Dust Mite-Allergic Patients
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DOI：
10.4168/aair.2019.11.3.330
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发表时间：
2019-05-01
影响因子：
4.4
通讯作者：
Chabowski, Adrian
中科院分区：
文献类型：
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作者：
Kowal, Krzysztof;Zebrowska, Ewa;Chabowski, Adrian
目的：鞘磷脂在细胞生长、存活、炎症和组织重塑中发挥重要作用。屋尘螨(HDM)过敏是哮喘的主要危险因素。该研究的目的是评估过敏性哮喘表型是否与鞘脂代谢改变有关。方法：22例HDM过敏性哮喘患者和11例HDM过敏性鼻炎患者接受生物标准化屋尘螨提取物的支气管内激发。分别在激发前、激发后早期哮喘反应(EAR)、晚期哮喘反应(LAR)和激发后24小时采集全血和血小板贫乏血浆样本。结果：在所有尘螨过敏患者(HDM-AP)中，基础肺功能和气道高反应性(AHR)与血浆S1P和SFA1P浓度显著相关。呼出一氧化氮浓度与SFA和神经酰胺相关，但与S1P或SFA1P浓度无关。变应原激发使耳部血浆S1P浓度升高，但仅限于同时发生耳部和LAR的患者。在EAR期间测定的升高幅度与随后发生的LAR的严重程度相关。血小板和嗜酸性粒细胞计数是血浆S1P浓度的独立预测因子。仅在无哮喘反应的HDM-AP患者中，血浆SFA浓度显著升高。结论：HDM-AP患者的鞘脂代谢异常，S1P合成增强，新生鞘磷脂合成受阻，可能参与了HDM-AP的哮喘表型的形成。
Purpose: Sphingolipids play an important role in cell growth, survival, inflammation and tissue remodeling. House dust mite (HDM) allergy is a major risk factor for asthma. The aim of the study was to evaluate if allergic asthma phenotype is associated with altered sphingolipid metabolism.Methods: Twenty-two HDM-allergic asthmatic patients and 11 HDM-allergic rhinitis patients were challenged intrabronchially with biologically standardized Dermatophagoides pteronyssinus extract. Whole blood and platelet-poor plasma samples were collected before, during early asthmatic response (EAR), late asthmatic response (LAR) and 24 hours after the challenge. Concentrations of sphinganine (SFA), sphinganine-1-phosphate (SFA1P), ceramide, sphingosine (SFO) and sphingosine-1-phosphate (S1P) were measured using high performance liquid chromatography.Results: In all house dust mite-allergic patients (HDM-APs), baseline lung function and severity of airway hyperreactivity (AHR) correlated significantly with plasma S1P and SFA1P concentrations. Exhaled nitric oxide concentration, however, correlated with SFA and ceramide, but not with S1P or SFA1P concentration. Allergen challenge increased plasma S1P concentration during EAR, but only in patients who developed both EAR and LAR. The magnitude of the increase determined during EAR correlated with the severity of subsequently developed LAR. Platelet and eosinophil counts were independent predictors of plasma S1P concentration. A significant increase in plasma SFA concentration in response to allergen challenge was seen only in patients who did not develop asthmatic response.Conclusions: Altered sphingolipid metabolism, with augmented synthesis of S1P and impaired de novo sphingolipid synthesis in response to allergen challenge, may participate in the development of asthma phenotype in HDM-APs.