Involvement of mast cells in eosinophilic esophagitis.
Involvement of mast cells in eosinophilic esophagitis.
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DOI：
10.1016/j.jaci.2010.04.009
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发表时间：
2010-07
影响因子：
14.2
通讯作者：
Rothenberg, Marc E.
中科院分区：
文献类型：
--
作者：
Abonia, J. Pablo;Blanchard, Carine;Butz, Bridget Buckmeier;Rainey, Heather F.;Collins, Margaret H.;Stringer, Keith;Putnam, Philip E.;Rothenberg, Marc E.
嗜酸性食管炎（EE）是一种新兴的疾病，其发病机制尚不清楚。鉴于先前的研究主要集中在嗜酸性粒细胞在疾病诊断和发病机制中的作用，本研究调查了肥大细胞的参与。总的和脱颗粒的肥大细胞计数与微阵列和RT-PCR数据相关，以生成与EE患者和正常对照中的肥大细胞数量和脱颗粒相关的转录组表达谱。食管肥大细胞增多症和肥大细胞脱颗粒在EE患者与对照组相比明显（p < 0.01），这通过总肥大细胞染色和细胞外肥大细胞类胰蛋白酶的存在来评估（p < 0.01）。微阵列分析显示，肥大细胞水平与基因组的0.8%（301个基因）的失调相关，这些基因与组织嗜酸性粒细胞增多相关的基因部分不同。肥大细胞蛋白酶羧肽酶A3（CPA 3）和类胰蛋白酶，但不糜蛋白酶的转录本的表达，与肥大细胞水平和区别EE患者从控制。基底动脉上肥大细胞计数（p < 0.01）和脱颗粒（p < 0.01）与KIT配体mRNA表达成正比。用吞服丙酸氟替卡松（FP）治疗EE患者使应答患者中肥大细胞和肥大细胞相关转录组的水平正常化。在此，我们已经确定了EE患者食管中的局部肥大细胞增多症和肥大细胞脱粒;确定了食管肥大细胞相关转录组，其与嗜酸性粒细胞相关转录组显著不同，CPA 3 mRNA水平作为最佳肥大细胞替代标记物;并提供了KIT配体参与EE发病机制的证据。
Eosinophilic esophagitis (EE) is an emerging disorder with poorly understood pathogenesis. Whereas prior studies have primarily focused on the role of eosinophils in disease diagnosis and pathogenesis, this study investigates the involvement of mast cells. Total and degranulated mast cell counts were correlated to microarray and RT-PCR data to generate transcriptome expression profiles related to mast cell number and degranulation in EE patients and normal controls. Esophageal mastocytosis and mast cell degranulation was readily apparent in EE patients compared with controls (p < 0.01) as assessed by staining for total mast cells and the presence of extracellular mast cell tryptase (p < 0.01). Microarray analysis revealed that mast cell levels correlated with the dysregulation of 0.8% (301 genes) of the genome which were partially distinct from the genes that correlated with tissue eosinophilia. The expression of transcripts for the mast cell proteases carboxypeptidase A3 (CPA3) and tryptase, but not chymase, correlated with mast cell levels and distinguished EE patients from controls. Suprabasilar mast cell counts (p < 0.01) and degranulation (p < 0.01) were proportional with KIT ligand mRNA expression. Treatment of EE patients with swallowed fluticasone propionate (FP) normalized levels of mast cells and the mast cell related transcriptome in responder patients. Herein we have identified local mastocytosis and mast cell degranulation in the esophagus of EE patients; identified an esophageal mast cell associated transcriptome that is significantly divergent from the eosinophil-associated transcriptome with CPA3 mRNA levels serving as the best mast cell surrogate marker; and provide evidence for the involvement of KIT ligand in the pathogenesis of EE.
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影响因子：
29.4
作者：
Konikoff, Michael R.;Noel, Richard J.;Rothenberg, Marc E.
通讯作者：
Rothenberg, Marc E.
影响因子：
14.2
作者：
Assa'ad, Amal H.;Putnam, Philip E.;Rothenberg, Marc E.
通讯作者：
Rothenberg, Marc E.
影响因子：
12.6
作者：
Collins, Margaret H.;Blanchard, Carine;Rothenberg, Marc E.
通讯作者：
Rothenberg, Marc E.
影响因子：
4.4
作者：
Friend, DS;Gurish, MF;Stevens, RL
通讯作者：
Stevens, RL
影响因子：
4.4
作者：
Caughey, GH;Raymond, WW;Verghese, GM
通讯作者：
Verghese, GM