Platelet Activation, P-Selectin, and Eosinophil β1-Integrin Activation in Asthma
Platelet Activation, P-Selectin, and Eosinophil β1-Integrin Activation in Asthma
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DOI：
10.1164/rccm.201109-1712oc
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发表时间：
2012-03-01
影响因子：
24.7
通讯作者：
Mosher, Deane F.
中科院分区：
文献类型：
--
作者：
Johansson, Mats W.;Han, Shih-Tsung;Mosher, Deane F.
基本原理：在非严重过敏性哮喘受试者中，嗜酸性粒细胞β 1-整合素活化与FEV 1呈负相关，与嗜酸性粒细胞结合的P-选择素呈正相关。目的：确定不同严重程度哮喘受试者中β 1-整合素活化与肺功能或嗜酸性粒细胞结合的P-选择素之间的关系，并辨别嗜酸性粒细胞结合的P-选择素的来源。通过流式细胞术测定血液中嗜酸性粒细胞和血小板上的P-选择素和活化的β（1）-整合素。用ELISA法分析血浆中可溶性P-选择素、血小板因子4和血小板反应素-1。测量和主要结果：在所有哮喘患者中，活化β 1-整合素与嗜酸性粒细胞结合的P-选择素相关，尽管非重度哮喘患者的活化β 1-整合素高于重度哮喘患者。仅在非重度哮喘的年轻受试者中，活化β 1整合素与FVC校正的FEV 1呈负相关。奇怪的是，血小板表面P-选择素，一种血小板活化标志物，在严重哮喘患者中较低，而血浆血小板因子4，第二种血小板活化标志物，较高。相关性表明与嗜酸性粒细胞复合的P-选择素阳性血小板是与β（1）-整合素活化相关的嗜酸性粒细胞结合的P-选择素的主要来源。非重度哮喘患者接受全肺抗原激发后，已知可引起血小板活化的哮喘急性发作模型、循环嗜酸性粒细胞携带P-选择素和活化的β 1-整合素消失。结论：嗜酸性粒细胞β 1-整合素活化与肺功能之间的关系仅在非重度哮喘的年轻受试者中复制。然而，我们推断，血小板活化和活化的血小板与嗜酸性粒细胞结合，随后是P-选择素介导的嗜酸性粒细胞β（1）-整合素活化，在非重度和重度哮喘中均发生，在更严重的疾病中，血小板-嗜酸性粒细胞复合物快速移动到肺中。
Rationale: Eosinophil beta(1)-integrin activation correlates inversely with FEV1 and directly with eosinophil-bound P-selectin in subjects with nonsevere allergic asthma.Objectives: Determine the relationships between beta(1)-integrin activation and pulmonary function or eosinophil-bound P-selectin in subjects with asthma of varying severity and discern the source of eosinophil-bound P-selectin.Methods: Blood was assayed by flow cytometry for P-selectin and activated beta(1)-integrin on eosinophils and platelets. Plasma was analyzed with ELISA for soluble P-selectin, platelet factor 4, and thrombospondin-1.Measurements and Main Results: Activated beta(1)-integrin correlated with eosinophil-bound P-selectin among all subjects with asthma even though activated beta(1)-integrin was higher in subjects with nonsevere asthma than severe asthma. Activated beta(1)-integrin correlated inversely with FEV1 corrected for FVC only in younger subjects with nonsevere asthma. Paradoxically, platelet surface P-selectin, a platelet activation marker, was low in subjects with severe asthma, whereas plasma platelet factor 4, a second platelet activation marker, was high. Correlations indicated that P-selectin-positive platelets complexed to eosinophils are the major source of the eosinophil-bound P-selectin associated with beta(1)-integrin activation. After whole-lung antigen challenge of subjects with nonsevere asthma, a model of asthma exacerbation known to cause platelet activation, circulating eosinophils bearing P-selectin and activated beta(1)-integrin disappeared.Conclusions: The relationship between eosinophil beta(1)-integrin activation and pulmonary function was replicated only for younger subjects with nonsevere asthma. However, we infer that platelet activation and binding of activated platelets to eosinophils followed by P-selectin-mediated eosinophil beta(1)-integrin activation occur in both nonsevere and severe asthma with rapid movement of platelet-eosinophil complexes into the lung in more severe disease.