Johansson Mats W
Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI, United States.
Front Med (Lausanne). 2017 Jun 12;4:75. doi: 10.3389/fmed.2017.00075. eCollection 2017.
Asthma is frequently characterized by eosinophil-rich airway inflammation. Airway eosinophilia is associated with asthma exacerbations and likely plays a part in airway remodeling. Eosinophil recruitment from the bloodstream depends on circulating eosinophils becoming activated, which leads to eosinophil arrest on activated endothelium, extravasation, and continued movement through the bronchial tissue by interaction with the extracellular matrix (ECM). Circulating eosinophils can exist at different activation levels, which include non-activated or pre-activated (sensitized or "primed"). Further, the bloodstream may lack pre-activated cells, due to such eosinophils having arrested on endothelium or extravasated into tissue. Increased expression, and in some instances, decreased expression of cell-surface proteins, including CD44, CD45, CD45R0, CD48, CD137, neuropeptide S receptor, cytokine receptors, Fc receptors, and integrins (receptors mediating cell adhesion and migration by interacting with ligands on other cells or in the ECM), and activated states of integrins or Fc receptors on blood eosinophils have been reported to correlate with aspects of asthma. A subset of these proteins has been reported to respond to intervention, e.g., with anti-interleukin (IL)-5. How these surface proteins and the activation state of the eosinophil respond to other interventions, e.g., with anti-IL-4 receptor alpha or anti-IL-13, is unknown. Eosinophil surface proteins suggested to be biomarkers of activation, particularly integrins, and reports on correlations between eosinophil activation and aspects of asthma are described in this review. Intermediate activation of beta1 and beta2 integrins on circulating eosinophils correlates with decreased pulmonary function, airway inflammation, or airway lumen eosinophils in non-severe asthma. The correlation does not appear in severe asthma, likely due to a higher degree of extravasation of pre-activated eosinophils in more severe disease. Bronchoalveolar lavage (BAL) eosinophils have highly activated integrins and other changes in surface proteins compared to blood eosinophils. The activation state of eosinophils in lung tissue, although likely very important in asthma, is largely unknown. However, some recent articles, mainly on mice but partly on human cells, indicate that tissue eosinophils may have a surface phenotype(s) different from that of sputum or BAL eosinophils.
哮喘通常的特征是气道富含嗜酸性粒细胞的炎症。气道嗜酸性粒细胞增多与哮喘发作相关，并且可能在气道重塑中起作用。嗜酸性粒细胞从血液中募集取决于循环中的嗜酸性粒细胞被激活，这会导致嗜酸性粒细胞在活化的内皮细胞上停滞、渗出，并通过与细胞外基质（ECM）相互作用在支气管组织中持续移动。循环中的嗜酸性粒细胞可以以不同的激活水平存在，包括未激活或预激活（致敏或“启动”）。此外，由于这些嗜酸性粒细胞已在内皮细胞上停滞或渗出到组织中，血液中可能缺乏预激活的细胞。据报道，细胞表面蛋白（包括CD44、CD45、CD45R0、CD48、CD137、神经肽S受体、细胞因子受体、Fc受体和整合素（通过与其他细胞或ECM上的配体相互作用介导细胞粘附和迁移的受体））表达的增加以及在某些情况下表达的减少，以及血液嗜酸性粒细胞上整合素或Fc受体的激活状态与哮喘的各个方面相关。据报道，这些蛋白质的一个子集对干预有反应，例如使用抗白细胞介素（IL）-5。这些表面蛋白和嗜酸性粒细胞的激活状态如何对其他干预作出反应，例如使用抗IL-4受体α或抗IL-13，尚不清楚。本综述描述了被认为是激活生物标志物的嗜酸性粒细胞表面蛋白，特别是整合素，以及关于嗜酸性粒细胞激活与哮喘各方面之间相关性的报道。循环嗜酸性粒细胞上β1和β2整合素的中度激活与非重度哮喘患者的肺功能下降、气道炎症或气道腔嗜酸性粒细胞增多相关。在重度哮喘中这种相关性不明显，可能是由于在更严重的疾病中预激活的嗜酸性粒细胞渗出程度更高。与血液嗜酸性粒细胞相比，支气管肺泡灌洗（BAL）嗜酸性粒细胞具有高度激活的整合素和表面蛋白的其他变化。肺组织中嗜酸性粒细胞的激活状态虽然在哮喘中可能非常重要，但在很大程度上尚不清楚。然而，最近的一些文章，主要是关于小鼠但部分是关于人类细胞的，表明组织嗜酸性粒细胞可能具有与痰液或BAL嗜酸性粒细胞不同的表面表型。
