Pleural mesothelial cells in pleural and lung diseases

Our plain-English summary of Pleural mesothelial cells in pleural and lung diseases, by H. Batra, V.B. Antony (Journal of Thoracic Disease, 2015).

The study

• Authors: H. Batra, V.B. Antony
• Journal: Journal of Thoracic Disease
• Published: 2015;7(6):964-80
• Type of article: Review
• Cited by: 71 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

During development, the mesoderm maintains a complex relationship with the developing endoderm giving rise to the mature lung. Pleural mesothelial cells (PMCs) derived from the mesoderm play a key role during the development of the lung. The pleural mesothelium differentiates to give rise to the endothelium and smooth muscle cells via epithelial-to-mesenchymal transition (EMT). An aberrant recapitulation of such developmental pathways can play an important role in the pathogenesis of disease processes such as idiopathic pulmonary fibrosis (IPF). The PMC is the central component of the immune responses of the pleura. When exposed to noxious stimuli, it demonstrates innate immune responses such as Toll-like receptor (TLR) recognition of pathogen associated molecular patterns as well as causes the release of several cytokines to activate adaptive immune responses. Development of pleural effusions occurs due to an imbalance in the dynamic interaction between junctional proteins, n-cadherin and β-catenin, and phosphorylation of adherens junctions between PMCs, which is caused in part by vascular endothelial growth factor (VEGF) released by PMCs. PMCs play an important role in defense mechanisms against bacterial and mycobacterial pleural infections, and in pathogenesis of malignant pleural effusion, asbestos related pleural disease and malignant pleural mesothelioma. PMCs also play a key role in the resolution of inflammation, which can occur with or without fibrosis. Fibrosis occurs as a result of disordered fibrin turnover and due to the effects of cytokines such as transforming growth factor-β, platelet-derived growth factor (PDGF), and basic fibroblast growth factor; which are released by PMCs. Recent studies have demonstrated a role for PMCs in the pathogenesis of IPF suggesting their potential as a cellular biomarker of disease activity and as a possible therapeutic target. Pleural-based therapies targeting PMCs for treatment of IPF and other lung diseases need further exploration.

In plain English

This review article by two authors from the University of Alabama at Birmingham summarized published research on pleural mesothelial cells, the cells that line the chest wall and lungs. It reported no new data and did not describe how the studies it discussed were chosen. It covered the roles of these cells in lung development, immune defense, fluid build-up around the lungs (pleural effusion), infection, cancer, pleural scarring and idiopathic pulmonary fibrosis. In its section on asbestos-related pleural disease, the review cited laboratory and animal work. That work reported that these cells released signals attracting white blood cells in the presence of crocidolite, and that they made the inflammatory signal IL-8 when stimulated by asbestos. It also reported that the cells took up asbestos fibers, which seemed to increase their production of fibronectin, a protein that may play a role in pleural scarring. The review described a cited study of 352 patients in which a cell change called periostin-triggered EMT was associated with the sarcomatoid type of malignant mesothelioma and with shorter survival. The authors concluded that these cells may be a marker of disease activity in idiopathic pulmonary fibrosis and a possible treatment target.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published laboratory, animal and human studies; no methods for selecting studies are described
• Who was studied: Not applicable: the article reviewed earlier studies of pleural mesothelial cells (cell cultures, animal models and patients) and enrolled no participants of its own
• Exposure: Many stimuli acting on pleural mesothelial cells (bacteria, mycobacteria, cancer cells, talc, growth factors). The asbestos section discusses asbestos in general and crocidolite specifically, and also carbon nanotubes
• Main results:
  • Cited work reported that asbestos directly stimulated pleural mesothelial cells to make IL-8, which the review says may help mediate asbestos-induced pleural inflammation
  • Cited work reported that pleural mesothelial cells take up (phagocytose) asbestos fibers, which seemed to stimulate fibronectin production that may play a role in pleural fibrosis
  • The review states that in mouse models, PDGF mediated fibroblast growth in the pleura after inhaled crocidolite asbestos fibers, and that antibodies against PDGF blocked this growth
  • High TGF-beta levels reported in empyema, tuberculous pleuritis and asbestos-related pleural effusions were taken by the review to suggest a role for TGF-beta in pleural fibrosis
  • Cited work reported that carbon nanotubes caused a length-dependent, asbestos-like inflammatory response
  • In a cited retrospective cohort of 352 patients, activation of periostin-triggered EMT was associated with the sarcomatoid histotype of malignant mesothelioma and with shorter survival
  • The review reports that high levels of activated HGF and c-Met had been observed in mesothelioma and correlated with disease relapse and poor prognosis
  • The authors summarized that pleural mesothelial cells play a pivotal role in pleural fibrosis through release of TGF-beta, PDGF, bFGF and HGF
• The authors' conclusion: The authors concluded that pleural mesothelial cells may represent a novel cellular biomarker of disease activity in idiopathic pulmonary fibrosis and a potential therapeutic target

Topics

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Mesoderm, Mesothelium, Idiopathic, Pulmonary Fibrosis, Pleura, Cytokine, Pleural Effusion.

Related studies

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• Pleural mesothelial cells stimulated by asbestos release chemotactic activity for neutrophils in vitro — V.B. Antony, C.L. Owen, et al. (1989)
• Peritoneal mesothelial hyperplasia associated with gynaecological disease: a potential diagnostic pitfall that is commonly associated with endometriosis — R. Oparka, W.G. McCluggage, et al. (2011)
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• Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappaB, and Akt in normal and malignant human mesothelial cells — M. Pacurari, X.J. Yin, et al. (2008)
• Programmed necrosis induced by asbestos in human mesothelial cells causes high-mobility group box 1 protein release and resultant inflammation — H. Yang, Z. Rivera, et al. (2010)

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