Accumulation of intraepithelial mast cells with a unique protease phenotype in T(H)2-high asthma.
Accumulation of intraepithelial mast cells with a unique protease phenotype in T(H)2-high asthma.
复制标题
DOI：
10.1016/j.jaci.2010.03.003
复制
发表时间：
2010-05
影响因子：
14.2
通讯作者：
Fahy, John V.
中科院分区：
文献类型：
--
作者：
Dougherty, Ryan H.;Sidhu, Sukhvinder S.;Raman, Kavita;Solon, Margaret;Solberg, Owen D.;Caughey, George H.;Woodruff, Prescott G.;Fahy, John V.
以前，我们发现肥大细胞类胰蛋白酶和羧肽酶A3（CPA 3）在哮喘患者气道上皮中差异表达。我们还发现，哮喘受试者可以分为2个亚组（“TH 2高”和“TH 2低”哮喘）的基础上的上皮细胞基因签名的TH 2细胞因子的活性。我们试图描述哮喘中的上皮内肥大细胞（IEMCs）。我们进行了基因表达谱上皮刷和肥大细胞数量的体视学定量支气管活检标本从健康对照组和哮喘受试者吸入皮质类固醇（ICS）治疗前后。我们还在培养的气道上皮细胞和肥大细胞中进行了基因表达和蛋白定量研究。通过无监督聚类分析，发现气道上皮肥大细胞基因表达与IL-13标签基因表达密切相关。肥大细胞基因表达水平与ICS肺功能改善呈正相关。与TH 2-低哮喘受试者或健康对照受试者相比，TH 2-高哮喘受试者的IEMC密度比正常高2倍（两种比较P = 0.015），这些细胞的特征是表达胰蛋白酶和CPA 3，但不表达糜蛋白酶。IL-13诱导的干细胞因子在培养的气道上皮细胞的表达，肥大细胞暴露于IL-13激活的上皮细胞的条件培养基显示下调糜蛋白酶，但类胰蛋白酶或CPA 3的表达没有变化。IEMC数量在TH 2高哮喘受试者中增加，具有不寻常的蛋白酶表型（类胰蛋白酶和CPA 3高，糜蛋白酶低），并预测对ICS的反应性。IL-13刺激上皮细胞产生干细胞因子可能解释了肥大细胞在TH 2高哮喘上皮中的积聚。
Previously, we found that mast cell tryptases and carboxypeptidase A3 (CPA3) are differentially expressed in the airway epithelium in asthmatic subjects. We also found that asthmatic subjects can be divided into 2 subgroups (“TH2 high” and “TH2 low” asthma) based on epithelial cell gene signatures for the activity of TH2 cytokines. We sought to characterize intraepithelial mast cells (IEMCs) in asthma. We performed gene expression profiling in epithelial brushings and stereology-based quantification of mast cell numbers in endobronchial biopsy specimens from healthy control and asthmatic subjects before and after treatment with inhaled corticosteroids (ICSs). We also performed gene expression and protein quantification studies in cultured airway epithelial cells and mast cells. By means of unsupervised clustering, mast cell gene expression in the airway epithelium related closely to the expression of IL-13 signature genes. The levels of expression of mast cell genes correlate positively with lung function improvements with ICSs. IEMC density was 2-fold higher than normal in subjects with TH2-high asthma compared with that seen in subjects with TH2-low asthma or healthy control subjects (P = .015 for both comparisons), and these cells were characterized by expression of tryptases and CPA3 but not chymase. IL-13 induced expression of stem cell factor in cultured airway epithelial cells, and mast cells exposed to conditioned media from IL-13–activated epithelial cells showed downregulation of chymase but no change in tryptase or CPA3 expression. IEMC numbers are increased in subjects with TH2-high asthma, have an unusual protease phenotype (tryptase and CPA3 high and chymase low), and predict responsiveness to ICSs. IL-13–stimulated production of stem cell factor by epithelial cells potentially explains mast cell accumulation in TH2-high asthmatic epithelium.
登录
查看更多内容
影响因子：
64.8
作者：
CEPEK, KL;SHAW, SK;BRENNER, MB
通讯作者：
BRENNER, MB
DOI：
10.1164/ajrccm.161.5.9908090
发表时间：
2000-05-01
影响因子：
24.7
作者：
Gauvreau, GM;Lee, JM;O'Byrne, PM
通讯作者：
O'Byrne, PM
DOI：
10.1164/ajrccm/147.3.697
发表时间：
1993-03-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
LAITINEN, LA;LAITINEN, A;HAAHTELA, T
通讯作者：
HAAHTELA, T
影响因子：
56.9
作者：
Metz, Martin;Piliponsky, Adrian M.;Galli, Stephen J.
通讯作者：
Galli, Stephen J.
影响因子：
10
作者：
Andersson, C. K.;Mori, M.;Erjefalt, J. S.
通讯作者：
Erjefalt, J. S.