过敏性哮喘加重中的气道纤维蛋白形成级联:炎症和重塑的意义
2022/10/17
摘要
背景：哮喘患者的气道重塑会导致肺功能下降，这很可能是空气过敏原暴露引起的反复加重的结果。暴露在气源性致敏原中会引发一种由生长因子、细胞因子和其他蛋白质介质调节的刻板反应。这会导致晚期过敏反应，其特征是血管通透性、激活白细胞的招募和气道结构细胞的激活。蛋白质介质的光谱及其功能尚不完全清楚。
方法：支气管肺泡灌洗液(BALF)样本来自12名志愿者，这些志愿者在过敏原的节段支气管刺激(SBP-Ag)后表现出强烈的嗜酸性粒细胞招募。我们使用高效液相色谱-高分辨率质谱(LC-MS/MS)对BALF中的蛋白质进行了系统的鉴定和定量，随后进行了通路分析和与气道生理学的相关性分析。
结果：对SBP-ag前后BALF蛋白丰度的两两分析显示，55个蛋白上调，103个蛋白下调。我们观察到止血/纤维蛋白凝块、血小板活化、脂蛋白组装、中性粒细胞脱颗粒蛋白和急性期炎症-气道重塑通路的蛋白质组的富集。F2和纤维蛋白原γ(FGG)的丰度与嗜酸性粒细胞数量相关，而SERPINA3与FeNO的变化呈负相关。凝血蛋白F2和KNG与气道重塑指标FN1呈负相关。有趣的是，FEV1较低的患者显示出不同的过敏原诱导的8种BALF蛋白模式，包括MUC1、警报蛋白(HSPB1)和肌动蛋白聚合因子。
结论：纤维蛋白形成级联、血小板活化和重构的蛋白质丰度与晚期白细胞数量和重构标志物相关。FEV1较低的患者对过敏原有明显的动态反应。
Airway fibrin formation cascade in allergic asthma exacerbation: implications for
inflammation and remodeling
Zhu YL, Esnault S, Ge Y, et al.
Abtract
BACKGROUND: Airway remodeling in patients with asthma, which leads to a decline in pulmonary function, is likely the result of repeated exacerbations often provoked by aeroallergen exposures. Aeroallergen exposure triggers a stereotypic response orchestrated by growth factor cytokines and other protein mediators. This results in a late-phase allergic reaction characterized by vascular permeability, recruitment of activated leukocytes, and activation of structural cells of the airway. The spectrum of protein mediators and their functions are incompletely understood.
METHODS：Bronchoalveolar lavage fluid (BALF) samples were obtained from 12 volunteers who exhibited robust eosinophilic recruitment following segmental bronchial provocation with allergen (SBP-Ag). We systematically identified and quantified proteins in BALF using high-performance liquid chromatography-high-resolution mass spectrometry (LC-MS/MS) followed by pathway analysis and correlations with airway physiology.
RESULTS：Pairwise analysis of protein abundance in BALF pre- vs post-SBP-Ag revealed that 55 proteins were upregulated and 103 proteins were downregulated. We observed enrichment of groups of proteins mapping to hemostasis/fibrin clot, platelet activation, lipoprotein assembly, neutrophil degranulation proteins, and acute-phase inflammation-airway remodeling pathways. The abundances of F2 and Fibrinogen gamma (FGG) correlated with eosinophil numbers, whereas SERPINA3 negatively correlated with change in FeNO. The coagulation proteins F2 and KNG negatively correlated with FN1 an index of airway remodeling. Interestingly, patients with lower FEV1 showed distinct allergen-induced patterns of 8 BALF proteins, including MUC1, alarmins (HSPB1), and actin polymerization factors.
CONCLUSIONS：Protein abundance of the fibrin formation cascade, platelet activation and remodeling are associated with late-phase leukocyte numbers and markers of remodeling. Patients with lower FEV1 have distinct dynamic responses to allergen.
背景：哮喘患者的气道重塑会导致肺功能下降，这很可能是空气过敏原暴露引起的反复加重的结果。暴露在气源性致敏原中会引发一种由生长因子、细胞因子和其他蛋白质介质调节的刻板反应。这会导致晚期过敏反应，其特征是血管通透性、激活白细胞的招募和气道结构细胞的激活。蛋白质介质的光谱及其功能尚不完全清楚。
方法：支气管肺泡灌洗液(BALF)样本来自12名志愿者，这些志愿者在过敏原的节段支气管刺激(SBP-Ag)后表现出强烈的嗜酸性粒细胞招募。我们使用高效液相色谱-高分辨率质谱(LC-MS/MS)对BALF中的蛋白质进行了系统的鉴定和定量，随后进行了通路分析和与气道生理学的相关性分析。
结果：对SBP-ag前后BALF蛋白丰度的两两分析显示，55个蛋白上调，103个蛋白下调。我们观察到止血/纤维蛋白凝块、血小板活化、脂蛋白组装、中性粒细胞脱颗粒蛋白和急性期炎症-气道重塑通路的蛋白质组的富集。F2和纤维蛋白原γ(FGG)的丰度与嗜酸性粒细胞数量相关，而SERPINA3与FeNO的变化呈负相关。凝血蛋白F2和KNG与气道重塑指标FN1呈负相关。有趣的是，FEV1较低的患者显示出不同的过敏原诱导的8种BALF蛋白模式，包括MUC1、警报蛋白(HSPB1)和肌动蛋白聚合因子。
结论：纤维蛋白形成级联、血小板活化和重构的蛋白质丰度与晚期白细胞数量和重构标志物相关。FEV1较低的患者对过敏原有明显的动态反应。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Clinical Proteomics, 2022, 19(1). doi: ARTN 1510.1186/s12014-022-09351-3）
（Clinical Proteomics, 2022, 19(1). doi: ARTN 1510.1186/s12014-022-09351-3）
Airway fibrin formation cascade in allergic asthma exacerbation: implications for
inflammation and remodeling
Zhu YL, Esnault S, Ge Y, et al.
Abtract
BACKGROUND: Airway remodeling in patients with asthma, which leads to a decline in pulmonary function, is likely the result of repeated exacerbations often provoked by aeroallergen exposures. Aeroallergen exposure triggers a stereotypic response orchestrated by growth factor cytokines and other protein mediators. This results in a late-phase allergic reaction characterized by vascular permeability, recruitment of activated leukocytes, and activation of structural cells of the airway. The spectrum of protein mediators and their functions are incompletely understood.
METHODS：Bronchoalveolar lavage fluid (BALF) samples were obtained from 12 volunteers who exhibited robust eosinophilic recruitment following segmental bronchial provocation with allergen (SBP-Ag). We systematically identified and quantified proteins in BALF using high-performance liquid chromatography-high-resolution mass spectrometry (LC-MS/MS) followed by pathway analysis and correlations with airway physiology.
RESULTS：Pairwise analysis of protein abundance in BALF pre- vs post-SBP-Ag revealed that 55 proteins were upregulated and 103 proteins were downregulated. We observed enrichment of groups of proteins mapping to hemostasis/fibrin clot, platelet activation, lipoprotein assembly, neutrophil degranulation proteins, and acute-phase inflammation-airway remodeling pathways. The abundances of F2 and Fibrinogen gamma (FGG) correlated with eosinophil numbers, whereas SERPINA3 negatively correlated with change in FeNO. The coagulation proteins F2 and KNG negatively correlated with FN1 an index of airway remodeling. Interestingly, patients with lower FEV1 showed distinct allergen-induced patterns of 8 BALF proteins, including MUC1, alarmins (HSPB1), and actin polymerization factors.
CONCLUSIONS：Protein abundance of the fibrin formation cascade, platelet activation and remodeling are associated with late-phase leukocyte numbers and markers of remodeling. Patients with lower FEV1 have distinct dynamic responses to allergen.
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