Sputum CD34+IL-5Rα+ cells increase after allergen -: Evidence for in situ eosinophilopoiesis
Sputum CD34+IL-5Rα+ cells increase after allergen -: Evidence for in situ eosinophilopoiesis
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DOI：
10.1164/rccm.200307-1004oc
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发表时间：
2004-03-01
影响因子：
24.7
通讯作者：
Sehmi, R
中科院分区：
文献类型：
--
作者：
Dorman, SC;Efthimiadis, A;Sehmi, R
发生过敏原诱导的气道高反应性和嗜酸性粒细胞增多的哮喘患者骨髓嗜酸性粒细胞谱系祖细胞增加。此外，在吸入过敏原24小时后以及过敏个体的支气管和鼻腔活检中，循环嗜酸性粒细胞/嗜碱性粒细胞cfu的数量较高。这些细胞可能经历原位嗜酸性粒细胞生成，表明在吸入过敏原后，祖细胞从骨髓运输到气道，提供持续的效应细胞来源。为了检验这种可能性，我们使用流式细胞术检测了哮喘过敏患者的诱导痰中CD34（+）和CD34(+)IL-5Ralpha（+）细胞，分别在基线和吸入过敏原和稀释剂后7和24小时。分离的早期应答者（n = 9）与双应答者（n = 9）进行对比，双应答者出现过敏原诱导的痰和血嗜酸性粒细胞增多和气道高反应性，并与正常对照者进行对比。在基线时，与哮喘患者相比，正常对照者的痰嗜酸性粒细胞和CD34（+）细胞明显减少。两组哮喘患者在吸入过敏原后7小时痰中CD34（+）细胞增加，仅在双应答组持续24小时，与痰中CD34(+)IL-5Ralpha（+）细胞、嗜酸性粒细胞和白细胞介素-5的持续增加相关。这些结果表明嗜酸性粒细胞祖细胞可以迁移到气道，并可能向嗜酸性粒细胞表型分化。
Eosinophil lineage-committed progenitors increase in the bone marrow of subjects with asthma developing allergen-induced airway hyperresponsiveness and eosinophilia. Also, higher numbers of circulating eosinophil/basophil cfu have been demonstrated 24 hours after allergen inhalation and in bronchial and nasal biopsies of allergic individuals. These cells may undergo in situ eosinophilopoiesis, suggesting that after allergen inhalation, progenitor cells traffic from the bone marrow to the airways, providing an ongoing source of effector cells. To examine this possibility, CD34(+) and CD34(+)IL-5Ralpha(+) cells were measured in induced sputum from allergic subjects with asthma at baseline and at 7 and 24 hours after allergen and diluent inhalation, using flow cytometry. Isolated early responders (n = 9) were contrasted to dual responders (n = 9), who develop allergen-induced sputum and blood eosinophilla and airway hyperresponsiveness, and to normal control subjects. At baseline, there were significantly fewer sputum eosinophils and CD34(+) cells in normal control subjects compared with subjects with asthma. Sputum CD34(+) cells increased at 7 hours after allergen inhalation in both groups of subjects with asthma, which was sustained at 24 hours in the dual responder group only, associated with sustained increases in sputum CD34(+)IL-5Ralpha(+) cells, eosinophils, and interleukin-5. These results indicate that eosinophil progenitors can migrate to the airways and may differentiate toward an eosinophilic phenotype.