CCL2 release by airway smooth muscle is increased in asthma and promotes fibrocyte migration

S. Singh, A. Sutcliffe, D. Kaur, S. Gupta, D. Desai, R. Saunders, C. Brightling (Leicester, United Kingdom)

Source: International Congress 2014 – Cell biology 2014
Session: Cell biology 2014
Session type: Thematic Poster Session
Number: 3848
Disease area: Airway diseases

Congress or journal article abstractE-poster

Abstract

Asthma is characterized by variable airflow obstruction, airway inflammation, airway hyper-responsiveness and airway remodeling. Airway smooth muscle hyperplasia is a feature of airway remodeling and contributes to bronchial wall thickening.We sought to investigate the expression levels of chemokines in primary cultures of airway smooth muscle cells from asthmatics and healthy controls and to assess whether differentially expressed chemokines a)promote fibrocyte migration and b)are increased in blood from subjects with asthma and in sputum samples from those asthmatics with bronchial wall thickening.Chemokines released by healthy and asthmatic primary airway smooth muscle were measured by MesoScale Discovery platform and the chemokine most highly expressed was confirmed by ELISA. Expression of its cognate chemokine receptor by fibrocytes was examined by immunofluorescence and flow cytometry. The role of this chemokine in fibrocyte migration towards airway smooth muscle was investigated by chemotaxis assays.CCL2 levels were elevated in primary airway smooth muscle supernatants from asthmatics compared to healthy controls (1880±329 versus 947±203 pg/106 cells,p=0.02). CCR2 was expressed on fibrocytes. Fibrocytes migrated towards recombinant CCL2 and airway smooth muscle supernatants. These effects were inhibited by CCL2 neutralisation. CCL2 levels were increased in blood from asthmatics compared to healthy controls (136±14 versus 78±11 pg/mL,p=0.002) and sputum CCL2 was elevated in asthmatics with bronchial wall thickening (p=0.008).Airway smooth muscle-derived CCL2 mediates fibrocyte migration and potentially contributes to the development of airway smooth muscle hyperplasia in asthma.


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S. Singh, A. Sutcliffe, D. Kaur, S. Gupta, D. Desai, R. Saunders, C. Brightling (Leicester, United Kingdom). CCL2 release by airway smooth muscle is increased in asthma and promotes fibrocyte migration. Eur Respir J 2014; 44: Suppl. 58, 3848

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