Disruption of iron homeostasis in mesothelial cells after talc pleurodesis

Our plain-English summary of Disruption of iron homeostasis in mesothelial cells after talc pleurodesis, by A.J. Ghio, J.M. Soukup, L.A. Dailey, et al (American Journal of Respiratory Cell and Molecular Biology, 2012).

The study

• Authors: A.J. Ghio, J.M. Soukup, L.A. Dailey, J.H. Richards, J.L. Turi, E.N. Pavlisko, V.L. Roggli
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 2012;46(1):80-6
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The mechanism for biological effects after exposure to particles is incompletely understood. One postulate proposed to explain biological effects after exposure to particles involves altered iron homeostasis in the host. The fibro-inflammatory properties of mineral oxide particles are exploited therapeutically with the instillation of massive quantities of talc into the pleural space, to provide sclerosis. We tested the postulates that (1) in vitro exposure to talc induces a disruption in iron homeostasis, oxidative stress, and a biological effect, and (2) talc pleurodesis in humans alters iron homeostasis. In vitro exposures of both mesothelial and airway epithelial cells to 100 μg/ml talc significantly increased iron importation and concentrations of the storage protein ferritin. Using dichlorodihydrofluorescein, exposure to talc was associated with a time-dependent and concentration-dependent generation of oxidants in both cell types. The expression of proinflammatory mediators was also increased after in vitro exposures of mesothelial and airway epithelial cells to talc. Relative to control lung tissue, lung tissue from patients treated with sclerodesis demonstrated an accumulation of iron and increased expression of iron-related proteins, including ferritin, the importer divalent metal transport-1 and the exporter ferroportin-1. Talc was also observed to translocate to the parenchyma, and changes in iron homeostasis were focally distributed to sites of retention. We conclude that exposure to talc disrupts iron homeostasis, is associated with oxidative stress, and results in a biological effect (i.e., a fibro-inflammatory response). Talc pleurodesis can function as a model of the human response to mineral oxide particle exposure, albeit a massive one.

In plain English

This laboratory and tissue study examined talc used in pleurodesis, a treatment that places large amounts of talc into the space around the lung to seal it. No fibers were seen in the talc product. In a test without cells, talc picked up iron. In cell experiments, both mesothelial and airway lining cells exposed to talc accumulated iron, made more of the iron-storage protein ferritin, produced oxidants and released more of the inflammatory signal IL-8. Released IL-6 protein trended upward without statistical significance, while RNA for IL-8 and IL-6 increased. The authors also stained tissue removed from six men 2 to 15 months after talc pleurodesis; all but one had malignant mesothelioma. Controls were 12 tissue samples from patients with lung cancer or idiopathic pulmonary fibrosis. Control lungs showed no iron staining. Iron staining was found in all pleurodesis specimens, with strong staining for ferritin and two iron-transport proteins, talc particles within the lung, and sheets of collagen. The authors concluded that talc disrupts iron balance in these cells and is associated with oxidative stress and a biological effect.

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: Laboratory experiments on cultured human cells (mesothelial MeT-5A cells and BEAS-2B airway epithelial cells), combined with microscopic staining of human lung and pleural tissue removed at surgery, compared with control tissue
• Who was studied: The tissue study was done at Duke University Health System. Six surgical specimens came from patients who had talc pleurodesis 2 to 15 months earlier (mean 7 months, standard deviation 6), followed by extrapleural pneumonectomy. All six were male, with a mean age of 56 years (standard deviation 18). All but one had malignant mesothelioma; the exception had repeated pneumothoraces. Controls were men without pleurodesis: 6 pneumonectomy specimens from lung cancer patients (mean age 70) and 6 autopsy specimens from patients with idiopathic pulmonary fibrosis (mean age 68). No study dates were given.
• Exposure: The talc was Sclerosol (Bryan Corp.), used for pleurodesis. Electron microscopy showed mostly particles 10 to 50 micrometers across, made of magnesium and silicon, with no fibers seen. Cells were exposed to a single talc concentration, alone or with added iron (ferric ammonium citrate). Patients received talc by pleurodesis.
• Main results:
  • In a test without cells, ionizable iron measured 0.46 plus or minus 0.11 ppm for plain talc and 6.48 plus or minus 1.08 ppm for talc soaked in iron (talc–Fe). Talc–Fe produced a significantly greater oxidant signal than plain talc.
  • Mesothelial cells exposed to talc for 4 hours accumulated nonheme iron. Cell zinc did not change.
  • BEAS-2B airway epithelial cells exposed to talc showed similar increases in nonheme iron.
  • Ferritin increased in both mesothelial and airway epithelial cells after talc exposure.
  • Both mesothelial and BEAS-2B airway cells produced oxidants after talc exposure, and production increased with time and with talc concentration.
  • Both cell types released more IL-8 protein after talc exposure. Released IL-6 trended upward, but the difference was not statistically significant.
  • RNA for IL-8 and IL-6 increased after a 4-hour talc exposure in both mesothelial and BEAS-2B cells.
  • Control lung tissue showed no iron staining in the pleura or lung tissue. Iron staining was found in all six specimens taken after talc pleurodesis.
  • In pleurodesis patients, ferritin staining of the pleura was very strong. Staining for the iron importer DMT1 and the iron exporter FPN1 was greatly increased compared with controls.
  • In pleurodesis patients, talc particles were found inside the lung tissue, not only in the pleura.
  • Tissue from pleurodesis patients showed sheets of collagen on trichrome staining. Control lung cancer specimens showed only minuscule staining.
• The authors' conclusion: The authors concluded that talc exposure disrupts iron balance in mesothelial and airway epithelial cells and is associated with oxidative stress and a biological (fibro-inflammatory) effect, similar to other particles. They also concluded that the resulting iron accumulation and changes in iron-related proteins are seen in patients after pleurodesis.
• Limitations the authors state:
  • The authors stated that they did not identify the source of the iron that accumulated in cells exposed to talc.
  • The authors stated that evidence for disrupted iron balance in idiopathic pulmonary fibrosis was not compelling, and they did not propose this pathway for all fibrotic injuries.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Talc and vermiculite.

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Talc Pleurodesis, Talc, Oxidative Stress, Ferritin, Parenchyma.

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