Pathophysiology of the Pleura

Jantz, Michael A.; Antony, Veena B.

doi:10.1159/000113629

Cited by 111 publications

(88 citation statements)

References 142 publications

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“…Their primary purpose has been thought to be production of a lubricating layer of pleural fluid to facilitate expansion of the lung by reducing friction with the encasing musculoskeletal structures of the thorax. Their role in host defence and fighting infections, such as empyema, has also been well recognised [33]. However, despite the proximity to the pulmonary parenchyma, and despite subpleural patterns seen in several lung diseases, the pleura has been thought to be an innocent bystander in parenchymal disease.…”

Section: Discussionmentioning

confidence: 99%

Parenchymal trafficking of pleural mesothelial cells in idiopathic pulmonary fibrosis

Mubarak¹,

Montes-Worboys²,

Regev³

et al. 2011

Eur Respir J

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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)-b1. Mouse lungs were lavaged and examined for the presence of GFP, smooth muscle a-actin (a-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-b1 dose. Fluorescent staining showed a-SMA expression in GFP-expressing PMCs, with co-localisation of GFP and a-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.

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Section: Discussionmentioning

confidence: 99%

Parenchymal trafficking of pleural mesothelial cells in idiopathic pulmonary fibrosis

Mubarak¹,

Montes-Worboys²,

Regev³

et al. 2011

Eur Respir J

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“…Routine expiratory chest radiographs are useless [10]. It is important to realise that a contralateral shift of the trachea and mediastinum is a completely normal phenomenon in spontaneous pneumothorax, and not at all suggestive for tension pneumothorax; this observation should therefore in no way influence treatment strategies [1].…”

mentioning

confidence: 99%

Spontaneous pneumothorax: epidemiology, pathophysiology and cause

Noppen¹

2010

Eur Respir Rev

233

193

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“…It has become apparent that these cells play a central dynamic role in the control of injury and repair processes that take place in the pleural and other serosal tissues . Mesothelial cells are a unique cell type originating from mesoderm and vested with a number of important specialized functions including release of pro-and anti-inflammatory and other immunomodulatory mediators; secretion of factors that promote deposition and clearance of fibrin; and synthesis of growth factors and extracellular matrix proteins that aid in serosal repair (Jantz & Antony, 2008). Asbestos may injure pleural mesothelial cells either by direct or indirect mechanisms, including (1) injury by free radicals, (2) inflammasome activation, (3) alterations of intracellular signaling pathways, (4) release of cytokines and chemokines, (5) physical disruption of chromosomes, (6) alterations in growth factors, and (7) changes in coagulation and fibrinolysis pathways (Manning et al, 2002;Mutsaers et al, 2004;Robledo & Mossman, 1999).…”

Section: Mesothelial Cell Biology and Fiber Interactionsmentioning

confidence: 99%

Role of Macrophage-induced Inflammation in Mesothelioma

Broaddus¹

2012

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 5f. WORK UNIT NUMBER REPORT DATE July 2012 REPORT TYPE PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERUniversity of California San Francisco, CA 94143-0962 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTMacrophages are a major inflammatory cell in malignant pleural mesothelioma and may help maintain tumor resistance to therapy. In this final year, we have completed the key tasks that confirm the importance of the macrophage in the inflammatory cell environment of mesothelioma. We have confirmed that it is possible to alter the polarization of macrophages to either an M1 (anti-tumor) or M2 (pro-tumor) phenotype and that a shift toward the Th1 phenotype or depletion of macrophages increases mesothelioma cell apoptosis and chemosensitivity. In our orthotopic murine mesothelioma model, the depletion of macrophages increases the mesothelioma response to chemotherapy. We have recently used a non-toxic CSF1 receptor inhibitor already in clinical trials to manipulate macrophages and shown that the tumors become more responsive to chemotherapy regimens used in patients with mesothelioma. At the end of our three year award, we have convincing evidence that manipulation of macrophages can alter the response of mesothelioma to standard therapy. Our major publications on these findings are in preparation and an RO1 application with a clinical trial included is planned for submission this fall. SUBJECT TERMSNone provided. I. INTRODUCTIONInflammation is an early and consistent feature of mesothelioma [1, 2], an incurable tumor with a high level of resistance to chemotherapy [3]. Within this inflammatory milieu, we have discovered that there is a large population of macrophages, in a higher percentage than we have found in other thoracic malignancies. The macrophage is perhaps the earliest cell recruited to the asbestos...

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Pathophysiology of the Pleura

Cited by 111 publications

References 142 publications

Parenchymal trafficking of pleural mesothelial cells in idiopathic pulmonary fibrosis

Parenchymal trafficking of pleural mesothelial cells in idiopathic pulmonary fibrosis

Spontaneous pneumothorax: epidemiology, pathophysiology and cause

Role of Macrophage-induced Inflammation in Mesothelioma

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