Pulmonary toxicants and fibrosis: innate and adaptive immune mechanisms

Our plain-English summary of Pulmonary toxicants and fibrosis: innate and adaptive immune mechanisms, by R. Malaviya, H.M. Kipen, R. Businaro, et al (Toxicology and Applied Pharmacology, 2020).

The study

• Authors: R. Malaviya, H.M. Kipen, R. Businaro, J.D. Laskin, D.L. Laskin
• Journal: Toxicology and Applied Pharmacology
• Published: 2020;409:115272
• Type of article: Review
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Pulmonary fibrosis is characterized by destruction and remodeling of the lung due to an accumulation of collagen and other extracellular matrix components in the tissue. This results in progressive irreversible decreases in lung capacity, impaired gas exchange and eventually, hypoxemia. A number of inhaled and systemic toxicants including bleomycin, silica, asbestos, nanoparticles, mustard vesicants, nitrofurantoin, amiodarone, and ionizing radiation have been identified. In this article, we review the role of innate and adaptive immune cells and mediators they release in the pathogenesis of fibrotic pathologies induced by pulmonary toxicants. A better understanding of the pathogenic mechanisms underlying fibrogenesis may lead to the development of new therapeutic approaches for patients with these debilitating and largely irreversible chronic diseases.

Copyright © 2020. Published by Elsevier Inc.

In plain English

This was a narrative review, not a study of patients or animals. The authors described how cells of the innate and adaptive immune system (macrophages, neutrophils, fibrocytes, T lymphocytes and myeloid-derived suppressor cells) and the mediators they release contribute to lung fibrosis caused by toxicants including bleomycin, asbestos, silica, nanoparticles, mustard vesicants and ionizing radiation, and they tabulated published rodent models. For asbestos, the review stated that asbestos is the common name for six naturally occurring silicate mineral fibers, occurring as serpentine (chrysotile) and amphibole forms, and that prolonged inhalation of more than 10 years is associated with diffuse interstitial pulmonary fibrosis (asbestosis), noted in occupational settings and in cohabitants of exposed workers. The authors described asbestos-induced activation of alveolar macrophages that take up the fibers, upregulation of inducible nitric oxide synthase with production of reactive nitrogen and oxygen species, release of cytokines and chemokines, and, with long-term exposure, profibrotic cytokines and accumulation of extracellular matrix proteins facilitated by PDGF and TGF-beta. Rodent models of asbestos inhalation and intratracheal instillation were tabulated. The authors concluded that effective antifibrotic therapy will likely require a multidimensional approach.

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 innate and adaptive immune mechanisms in toxicant-induced pulmonary fibrosis
• Who was studied: No new patients or animals studied; the review drew on published human studies (e.g. idiopathic pulmonary fibrosis patients) and established rodent models of pulmonary fibrosis
• Exposure: Fibrogenic pulmonary toxicants reviewed: bleomycin, asbestos (chrysotile and amphiboles including crocidolite), silica, nanoparticles, mustard vesicants and ionizing radiation
• Main results:
  • The review described asbestos as six silicate mineral fibers of serpentine (chrysotile) and amphibole type
  • The review stated that prolonged inhalation of asbestos (more than 10 years) is associated with asbestosis
  • The review stated asbestosis has been seen in workers and in people living with exposed workers
  • Mechanism described for asbestos: alveolar macrophages take up asbestos particles
  • This was described as leading to iNOS upregulation and increased reactive nitrogen and oxygen species
  • Long-term asbestos exposure was described as leading to profibrotic cytokines and extracellular matrix accumulation in lung and fibrotic lesions
  • The review reported a suggested role for iron on the asbestos fiber surface, since a scavenger or iron chelator attenuated fibrotic effects in rodent lung
  • Rodent models of asbestos inhalation or intratracheal instillation were tabulated (Table 2)
  • The review contrasted silica pathology with asbestos, describing nodules with a hyaline center
  • On treatment, the review reported that trials of antioxidants, TNF-alpha inhibitors, IFN-gamma or bosentan showed no significant improvement in IPF patients
• The authors' conclusion: The authors concluded that fibrogenesis is a complex multi-cell process and that effective antifibrotic therapy will likely need to target both inflammatory cell activation and the tissue microenvironment
• Limitations the authors state:
  • The authors stated the role of regulatory T cells in lung fibrosis is unclear, with both profibrotic and antifibrotic activities reported
  • The authors stated the role of MMPs and TIMPs in tissue remodeling is complex and depends on the toxicant and microenvironment
  • The authors noted that mechanisms of silicosis differ between rodent species

Topics

Medical terms in this study, explained in our Lexicon: Fibrosis, Pulmonary Fibrosis, Collagen.

Related studies

• Role of Macrophages in Acute Lung Injury and Chronic Fibrosis Induced by Pulmonary Toxicants — D.L. Laskin, R. Malaviya, et al. (2019)
• Genes involved in innate immunity associated with asbestos-related fibrotic changes — M.K. Kukkonen, T. Vehmas, et al. (2014)
• Bronchoalveolar lavage in pulmonary fibrosis: comparison of cells obtained with lung biopsy and clinical features — P.L. Haslam, C.W. Turton, et al. (1980)
• Epithelial-mesenchymal transition involved in pulmonary fibrosis induced by multi-walled carbon nanotubes via TGF-beta/Smad signaling pathway — T. Chen, H. Nie, et al. (2014)
• Response of mouse lung to crocidolite asbestos. 2. Pulmonary fibrosis after long fibres — I.Y. Adamson, D.H. Bowden (1987)
• Pulmonary function and pleural fibrosis: quantitative relationships with an integrative index of pleural abnormalities — R. Lilis, A. Miller, et al. (1991)

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