哮喘联盟

   摘要
   背景：重症哮喘患者对糖皮质激素治疗的敏感性较普通哮喘患者低，并且气道重构表现增强。间充质祖细胞-成纤维细胞可能参与了哮喘气道的重构。我们推测重症哮喘的成纤维细胞与非重症哮喘的成纤维细胞不同。
   目的：验证重症哮喘患者和非重症哮喘患者血中纤维细胞的存活时间、肌纤维母细胞分化以及C-C趋化因子受体的表达，并且研究激素对成纤维细胞功能的影响。
   方法：分别从健康受试者、患有非重症和重症哮喘血液中分离非粘附、非T细胞的单个核细胞，应用流式细胞仪通过细胞表达CD45、胶原蛋白I、和α平滑肌肌动蛋白确定总的和分化的肌纤维母细胞。应用流式细胞仪测量CCR7及糖皮质激素受体的表达。
   结果：在重症哮喘患者中观察到循环纤维细胞增高，肌纤维母细胞分化比例增高。在健康受试者及非重症哮喘患者中，地塞米松介导的细胞凋亡引起了培养的纤维细胞和总的非粘附非T细胞的单个核细胞的减低，但是在重症哮喘患者中未观察到这一现象。地塞米松减低了非重症哮喘患者纤维细胞CCR7的表达，但不减低重症患者的表达。重症哮喘患者纤维细胞的糖皮质激素受体表达减低。
   结论：重症哮喘患者循环纤维细胞数量增加，这表明肌纤维母细胞分化能力增加，并且对糖皮质激素的反应性下降。
 

（林江涛 审校）
JAllergyClinImmunol.2014Dec6.pii:S0091-6749(14)01573-5.doi:10.1016/j.jaci.2014.10.031. [Epub ahead of print]

 

Increased phenotypic differentiation and reduced corticosteroid sensitivity of fibrocytes in severe asthma.
 

Lo CY1, Michaeloudes C2, Bhavsar PK2, Huang CD3, Wang CH3, Kuo HP3, Chung KF4.
 

ABSTRACT
BACKGROUND: Patients with severe asthma are less responsive to corticosteroid therapy and show increased airway remodeling. The mesenchymal progenitors, fibrocytes, may be involved in the remodeling of asthmatic airways. We propose that fibrocytes in severe asthma are different from those in nonsevere asthma.
OBJECTIVES: To examine the survival, myofibroblastic differentiation, and C-C chemokine receptor 7 (CCR7) expression in blood fibrocytes from patients with severe and nonsevere asthma and study the effect of corticosteroids on fibrocyte function.
METHODS: The nonadherent non-T-cell fraction of blood mononuclear cells was isolated from healthy subjects and patients with nonsevere and severe asthma. Total and differentiating fibrocytes were identified by their expression of CD45, collagen I, and α-smooth muscle actin using flow cytometry. The expression of CCR7 and of the glucocorticoid receptor was measured by using flow cytometry.
RESULTS: Increased numbers of circulating fibrocytes, with greater myofibroblastic differentiation potential, were observed in patients with severe asthma. Dexamethasone induced apoptosis, leading to reduction in the number of cultured fibrocytes and total nonadherent non-T cells from healthy subjects and patients with nonsevere asthma but not from patients with severe asthma. Dexamethasone reduced CCR7 expression in fibrocytes from patients with nonsevere asthma but not from patients with severe asthma. Glucocorticoid receptor expression was attenuated in fibrocytes from patients with severe asthma.
CONCLUSIONS: Patients with severe asthma have elevated numbers of circulating fibrocytes that show enhanced myofibroblastic differentiation and that are less responsive to the effects of corticosteroids.
 

JAllergyClinImmunol.2014Dec6.pii:S0091-6749(14)01573-5.doi:10.1016/j.jaci.2014.10.031. [Epub ahead of print]