CCL2 release by airway smooth muscle is increased in asthma and promotes fibrocyte migration..pdf (445.59 kB)
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CCL2 release by airway smooth muscle is increased in asthma and promotes fibrocyte migration.

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journal contribution
posted on 13.01.2016, 10:20 by S. R. Singh, Amanda Sutcliffe, D. Kaur, Sumit Gupta, D. Desai, Ruth Mary Saunders, Christopher E. Brightling
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 FCs 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 (CCL2) levels were increased in primary ASM supernatants from asthmatics compared with healthy controls. CCR2 was expressed on FCs. Fibrocytes migrated towards recombinant CCL2 and ASM supernatants. These effects were inhibited by CCL2 neutralization. CCL2 levels were increased in blood from asthmatics compared with healthy controls, and sputum CCL2 was increased in asthmatics with bronchial wall thickening. CONCLUSIONS: Airway smooth muscle-derived CCL2 mediates FC migration and potentially contributes to the development of ASM hyperplasia in asthma.

History

Citation

Allergy, 2014, 69 (9), pp. 1189-1197

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammation

Version

VoR (Version of Record)

Published in

Allergy

Publisher

Wiley

issn

0105-4538

eissn

1398-9995

Acceptance date

06/03/2014

Copyright date

2014

Available date

13/01/2016

Publisher version

http://onlinelibrary.wiley.com/doi/10.1111/all.12444/abstract

Language

en