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Fibrocyte localisation to the ASM bundle in asthma: bidirectional effects on cell phenotype and behaviour

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journal contribution
posted on 2020-11-25, 11:21 authored by Ruth Saunders, Davinder Kaur, Dhananjay Desai, Rachid Berair, Latifa Chachi, Richard D Thompson, Salman H Siddiqui, Christopher E Brightling
Objectives
Airway hyper‐responsiveness and persistent airflow obstruction contribute to asthma pathogenesis and symptoms, due in part to airway smooth muscle (ASM) hypercontractility and increased ASM mass. Fibrocytes have been shown to localise to the ASM in asthma however it is not known whether fibrocytes localise to the ASM in nonasthmatic eosinophilic bronchitis (NAEB) and chronic obstructive pulmonary disease (COPD). In addition, the potential consequences of fibrocyte localisation to ASM as regards asthma pathophysiology has not been widely studied.

Methods
Fibrocytes and proliferating cells were enumerated in ASM in bronchial tissue using immunohistochemistry. The effects of primary ASM and fibrocytes upon each other in terms of phenotype and behaviour following co‐culture were investigated by assessing cell number, size, apoptotic status, phenotype and contractility in in vitro cell‐based assays.

Results
Increased fibrocyte number in the ASM was observed in asthma versus NAEB, but not NAEB and COPD versus controls, and confirmed in asthma versus controls. ASM proliferation was not detectably different in asthmatics versus healthy controls in vivo. No difference in proliferation, apoptotic status or size of ASM was seen following culture with/without fibrocytes. Following co‐culture with ASM from asthmatics versus nonasthmatics, fibrocyte smooth muscle marker expression and collagen gel contraction were greater. Following co‐culture, fibrocyte CD14 expression was restored with the potential to contribute to asthma pathogenesis via monocyte‐mediated processes dependent on the inflammatory milieu.

Conclusion
Further understanding of mechanisms of fibrocyte recruitment to and/or differentiation within the ASM may identify novel therapeutic targets to modulate ASM dysfunction in asthma.

Funding

Asthma UK

Wellcome Senior Clinical Fellowship. Grant Number: WT082265

NIHR Leicester Biomedical Research Centre

History

Author affiliation

Department of Respiratory Sciences, University of Leicester

Version

  • VoR (Version of Record)

Published in

Clinical & Translational Immunology

Volume

9

Issue

11

Publisher

Wiley

issn

2050-0068

eissn

2050-0068

Acceptance date

2020-10-09

Copyright date

2020

Available date

2020-11-13

Language

en

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