The C-C motif chemokine ligands CCL5, CCL11, and CCL24 induce the migration of circulating fibrocytes from patients with severe asthma
The C-C motif chemokine ligands CCL5, CCL11, and CCL24 induce the migration of circulating fibrocytes from patients with severe asthma
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DOI：
10.1038/mi.2012.109
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发表时间：
2013-07-01
影响因子：
8
通讯作者：
Mattoli, S.
中科院分区：
文献类型：
--
作者：
Isgro, M.;Bianchetti, L.;Mattoli, S.
C-C基序趋化因子配体5 （CCL5）、CCL11和CCL24参与哮喘的发病，其功能主要与气道嗜酸性粒细胞的募集有关。本研究测试了它们诱导循环纤维细胞迁移的能力，这可能有助于严重哮喘中不可逆气流阻塞的发展。与非严重/治疗反应性哮喘（PwNSA）患者的SFP相比，来自严重/治疗难治性哮喘（PwSA）患者的痰液相（SFP）中CCL5、CCL11和CCL24的浓度升高。来自PwSA的循环纤维细胞表达这些趋化因子的受体水平升高，并在重组CCL5、CCL11和CCL24的作用下迁移。来自PwSA的SFP诱导了自体纤维细胞的迁移，其活性被内源性CCL5、CCL11和CCL24的中和显著减弱。这些发现提示CCL5、CCL11和CCL24可能参与重度哮喘患者气道纤维细胞的募集。
The C-C motif chemokine ligand 5 (CCL5), CCL11, and CCL24 are involved in the pathogenesis of asthma, and their function is mainly associated with the airway recruitment of eosinophils. This study tested their ability to induce the migration of circulating fibrocytes, which may contribute to the development of irreversible airflow obstruction in severe asthma. The sputum fluid phase (SFP) from patients with severe/treatment-refractory asthma (PwSA) contained elevated concentrations of CCL5, CCL11, and CCL24 in comparison with the SFP from patients with non-severe/treatment-responsive asthma (PwNSA). The circulating fibrocytes from PwSA expressed the receptors for these chemokines at increased levels and migrated in response to recombinant CCL5, CCL11, and CCL24. The SFP from PwSA induced the migration of autologous fibrocytes, and its activity was significantly attenuated by neutralization of endogenous CCL5, CCL11, and CCL24. These findings suggest that CCL5, CCL11, and CCL24 may contribute to the airway recruitment of fibrocytes in severe asthma.