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CCL 2 release by airway smooth muscle is increased in asthma and promotes fibrocyte migration
Author(s) -
Singh S. R.,
Sutcliffe A.,
Kaur D.,
Gupta S.,
Desai D.,
Saunders R.,
Brightling C. E.
Publication year - 2014
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12444
Subject(s) - chemokine , fibrocyte , immunology , asthma , medicine , airway , chemotaxis , sputum , chemokine receptor , cellular infiltration , inflammation , pathology , receptor , tuberculosis , surgery
Abstract Background Asthma is characterized by variable airflow obstruction, airway inflammation, airway hyper‐responsiveness and airway remodelling. Airway smooth muscle ( ASM ) hyperplasia is a feature of airway remodelling and contributes to bronchial wall thickening. We sought to investigate the expression levels of chemokines in primary cultures of ASM cells from asthmatics vs healthy controls and to assess whether differentially expressed chemokines (i) promote fibrocyte ( FC ) migration towards ASM and (ii) are increased in blood from subjects with asthma and in sputum samples from those asthmatics with bronchial wall thickening. Methods Chemokine concentrations released by primary ASM were measured by MesoScale Discovery platform. The chemokine most highly expressed by ASM from asthmatics compared with healthy controls was confirmed by ELISA , and expression of its cognate chemokine receptor by FC s was examined by immunofluorescence and flow cytometry. The role of this chemokine in FC migration towards ASM was investigated by chemotaxis assays. Results Chemokine ( C ‐ C motif) ligand 2 ( CCL 2) levels were increased in primary ASM supernatants from asthmatics compared with healthy controls. CCR 2 was expressed on FC s. Fibrocytes migrated towards recombinant CCL 2 and ASM supernatants. These effects were inhibited by CCL 2 neutralization. CCL 2 levels were increased in blood from asthmatics compared with healthy controls, and sputum CCL 2 was increased in asthmatics with bronchial wall thickening. Conclusions Airway smooth muscle‐derived CCL 2 mediates FC migration and potentially contributes to the development of ASM hyperplasia in asthma.