Defense and protection mechanisms in lung exposed to asbestiform fiber: the role of macrophage migration inhibitory factor and heme oxygenase-1

Our plain-English summary of Defense and protection mechanisms in lung exposed to asbestiform fiber: the role of macrophage migration inhibitory factor and heme oxygenase-1, by C. Loreto, R. Caltabiano, A.C.E. Graziano, et al (European Journal of Histochemistry, 2020).

The study

• Authors: C. Loreto, R. Caltabiano, A.C.E. Graziano, S. Castorina, C. Lombardo, V. Filetti, E. Vitale, G. Rapisarda, V. Cardile, C. Ledda, V. Rapisarda
• Journal: European Journal of Histochemistry
• Published: 2020;64(2)
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Fluoro-edenite (FE), an asbestiform fiber, is responsible for many respiratory pathologies: chronic obstructive diseases, pleural plaques, fibrosis, and malignant mesothelioma. Macrophage migration inhibitory factor (MIF) is one of the first cytokines produced in response to lung tissue damage. Heme oxygenase-1 (HO-1) is a protein with protective effects against oxidative stress. It is up regulated by several stimuli including pro-inflammatory cytokines and factors that promote oxidative stress. In this research, the in vivo model of sheep lungs naturally exposed to FE was studied in order to shed light on the pathophysiological events sustaining exposure to fibers, by determining immunohistochemical lung expression of MIF and HO-1. Protein levels expression of HO-1 and MIF were also evaluated in human primary lung fibroblasts after exposure to FE fibers in vitro. In exposed sheep lungs, MIF and HO-1 immunoexpression were spread involving the intraparenchymal stroma around bronchioles, interstitium between alveoli, alveolar epithelium and macrophages. High MIF immunoexpression prevails in macrophages. Similar results were obtained in vitro, but significantly higher values were only detected for HO-1 at concentrations of 50 and 100 μg/mL of FE fibers. MIF and HO-1 expressions seem to play a role in lung self-protection against uncontrolled chronic inflammation, thus counteracting the strong link with cancer development, induced by exposure to FE. Further studies will be conducted in order to add more information about the role of MIF and HO-1 in the toxicity FE-induced.

In plain English

This study examined fluoro-edenite, an asbestiform fiber from a stone quarry in Biancavilla, Sicily, and two proteins. MIF is produced after lung damage. HO-1 protects against oxidative stress. The authors studied lungs from 60 sheep randomly selected from flocks grazing 3 km from Biancavilla, and from 10 control sheep from a flock grazing about 50 km from the quarry. Fibers were scattered in the exposed sheep's lungs, and tissue changes were greater where fibers had settled. Non-exposed lungs showed only non-significant traces of either protein. The stained area for both proteins was much higher in exposed lungs (p less than 0.05), and MIF staining was particularly intense in macrophages (immune cells). The authors also exposed laboratory-grown human lung fibroblasts to fibers for 72 hours. HO-1 rose significantly at 50 and 100 µg/ml but not at 10 µg/ml. MIF showed only a weak, non-significant increase. The authors concluded that these proteins seem to play a role in the lung's self-protection against uncontrolled chronic inflammation. They said the relationship to pleural malignancies remains to be established.

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: Animal study of lungs from sheep naturally exposed to fluoro-edenite in the environment (tissue staining, immunohistochemistry), plus a laboratory experiment on human lung fibroblasts in culture
• Who was studied: 60 sheep of both sexes, randomly selected from six exposed flocks (360 sheep) grazing 3 km from Biancavilla, Sicily, Italy, and 10 control sheep from a flock (60 sheep) grazing about 50 km from the Biancavilla stone quarry; aged 4.0 to 6.5 years. Also primary normal human adult lung fibroblasts grown in the laboratory.
• Exposure: Fluoro-edenite (FE), an asbestiform fiber found as a contaminant at a stone quarry located in Biancavilla. The sheep were exposed naturally by grazing near Biancavilla. The human lung fibroblasts were exposed in the laboratory to 10, 50 and 100 µg/ml of FE fibers for 72 hours.
• Main results:
  • In exposed sheep, FE fibers were scattered in the lung tissue, and the tissue changes (including a fibrotic interstitium) were greater where fibers were deposited
  • In non-exposed sheep lungs, only non-significant traces of HO-1 and MIF staining were present
  • The percentage of lung area stained for HO-1 and MIF was very much higher in exposed sheep lungs than in non-exposed lungs (P<0.05)
  • In exposed sheep lungs, MIF was found in the stroma between the alveoli, around the bronchioles, and in macrophages
  • In exposed sheep lungs, the staining for MIF was particularly intense in macrophages
  • In human lung fibroblasts, HO-1 protein was significantly higher after exposure to 50 and 100 µg/ml of FE
  • In human lung fibroblasts, 10 µg/ml of FE produced a non-significant change in HO-1
  • In human lung fibroblasts, MIF was very low in untreated cells and increased only weakly and non-significantly with FE
• The authors' conclusion: The authors concluded that MIF and HO-1 expression seem to play a role in lung self-protection against uncontrolled chronic inflammation, thus counteracting the link with cancer development
• Limitations the authors state:
  • The authors stated that the relationship between these results and the development of pleural malignancies remains to be established
  • The MIF finding in sheep was not reproduced in the cell cultures. The authors suggested that in the living lung a more complex interaction between different cell types is involved.
  • The authors said further studies are planned on monocyte/macrophage cell lines

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis.

Medical terms in this study, explained in our Lexicon: Asbestiform, Macrophage, fluoro-edenite, Pleural Plaques, Fibrosis, Malignant Mesothelioma, Cytokine, Oxidative Stress.

Related studies

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• Expression of heme oxygenase-1 in the lungs of rats exposed to crocidolite asbestos — H. Nagatomo, Y. Morimoto, et al. (2005)
• Change of heme oxygenase-1 expression in lung injury induced by chrysotile asbestos in vivo and in vitro — H. Nagatomo, Y. Morimoto, et al. (2007)
• Expression of heme oxygenase-1 in the lungs of rats exposed to potassium octatitanate whiskers — Y. Obata, Y. Morimoto, et al. (2011)
• Angiogenesis correlates with macrophage and mast cell infiltration in lung tissue of animals exposed to fluoro-edenite fibers — G. Musumeci, C. Loreto, et al. (2016)
• Prevalence of anti-nuclear autoantibodies in subjects exposed to natural asbestiform fibers: a cross-sectional study — C. Ledda, R. Caltabiano, et al. (2018)

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