Document Detail


Clara cells inhibit alveolar epithelial wound repair via TRAIL-dependent apoptosis.
MedLine Citation:
PMID:  22790912     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Clara cells participate in bronchiolar wound repair and regeneration. Located in the bronchioles they become activated during alveolar injury in idiopathic pulmonary fibrosis (IPF) and migrate into the affected alveoli - a process called alveolar bronchiolisation. The purpose of this migration and their role in alveolar wound repair is controversial. This study was undertaken to investigate the role of Clara cells in alveolar epithelial wound repair and pulmonary fibrosis.A direct-contact co-culture in vitro model was utilised to evaluate the role of Clara cells (H441 cell line) on alveolar epithelial cell (AEC) (A549 cell line) and small airway epithelial cell (SAEC) wound repair. Immunohistochemistry was conducted on lung tissue samples from patients with IPF to replicate the in vitro findings ex vivo.Our studies demonstrate that Clara cells induce apoptosis in AECs and SAECs through a TRAIL-dependent mechanism resulting in significant inhibition of wound repair. Furthermore in the IPF lungs, TRAIL-expressing Clara cells were detected within the affected alveolar epithelia in areas of established fibrosis, together with widespread AEC apoptosis.From these findings, we hypothesise that the extensive pro-fibrotic remodelling associated with IPF could be driven by TRAIL-expressing Clara cells inducing apoptosis in AEC through a TRAIL-dependent mechanism.
Authors:
K M Akram; N J Lomas; M A Spiteri; N R Forsyth
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-12
Journal Detail:
Title:  The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology     Volume:  -     ISSN:  1399-3003     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8803460     Medline TA:  Eur Respir J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
School of Postgraduate Medicine, Keele University, Stoke-on-Trent, Staffordshire, ST4 7QB, UK.
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