title: Parenchymal trafficking of pleural mesothelial cells in idiopathic pulmonary fibrosis.
abstract: Idiopathic pulmonary fibrosis (IPF) is characterised by myofibroblast proliferation leading to architectural destruction. Neither the origin nor the continued proliferation of myofibroblasts is well understood. Explanted human IPF lungs were stained by immunohistochemistry for calretinin, a marker of pleural mesothelial cells (PMCs). Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) lungs acted as controls. The number of PMCs per 100 nucleated cells and per photomicrograph was estimated along with the Ashcroft score of fibrosis. Mouse PMCs expressing green fluorescent protein (GFP) or labelled with nanoparticles were injected into the pleural space of mice given intranasal transforming growth factor (TGF)-β1. Mouse lungs were lavaged and examined for the presence of GFP, smooth muscle α-actin (α-SMA) and calretinin. Calretinin-positive PMCs were found throughout IPF lungs, but not in COPD or CF lungs. The number of PMCs correlated with the Ashcroft score. In mice, nanoparticle-laden PMCs were recoverable by bronchoalveolar lavage, depending on the TGF-β1 dose. Fluorescent staining showed α-SMA expression in GFP-expressing PMCs, with co-localisation of GFP and α-SMA. PMCs can traffic through the lung and show myofibroblast phenotypic markers. PMCs are present in IPF lungs, and their number correlates with IPF severity. Since IPF presumably begins subpleurally, PMCs could play a pathogenetic role via mesothelial-mesenchymal transition.
authors: Division of Pulmonary, Critical Care Medicine and Sleep Medicine, Dept of Medicine, College of Medicine, University of Florida, USA. kamal.mubarak@gmail.com
authors: K K
authors: KK
authors: Mubarak
authors: A
authors: A
authors: Montes-Worboys
authors: D
authors: D
authors: Regev
authors: N
authors: N
authors: Nasreen
authors: K A
authors: KA
authors: Mohammed
authors: I
authors: I
authors: Faruqi
authors: E
authors: E
authors: Hensel
authors: M A
authors: MA
authors: Baz
authors: O A
authors: OA
authors: Akindipe
authors: S
authors: S
authors: Fernandez-Bussy
authors: S D
authors: SD
authors: Nathan
authors: V B
authors: VB
authors: Antony
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D064032:Calbindin 2; D002467:Cell Nucleus / Q000378:metabolism; D002648:Child; D003550:Cystic Fibrosis / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D004848:Epithelium / Q000473:pathology*; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D008168:Lung / Q000378:metabolism*; D008297:Male; D000090204:Mesothelin; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D058628:Myofibroblasts / Q000166:cytology; D010994:Pleura / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000097:blood*
chemical_list: C576764:CALB2 protein, human; C576511:Calb2 protein, mouse; D064032:Calbindin 2; D058851:GPI-Linked Proteins; D064030:S100 Calcium Binding Protein G; D000090204:Mesothelin