Mechanisms of action of inhaled fibers, particles and nanoparticles in lung and cardiovascular diseases

Our plain-English summary of Mechanisms of action of inhaled fibers, particles and nanoparticles in lung and cardiovascular diseases, by B.T. Mossman, P.J. Borm, V. Castranova, et al (Particle and Fibre Toxicology, 2007).

The study

• Authors: B.T. Mossman, P.J. Borm, V. Castranova, D.L. Costa, K. Donaldson, S.R. Kleeberger
• Journal: Particle and Fibre Toxicology
• Published: 2007;4:4
• Type of article: Editorial
• Cited by: 80 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: A symposium on the mechanisms of action of inhaled airborne particulate matter (PM), pathogenic particles and fibers such as silica and asbestos, and nanomaterials, defined as synthetic particles or fibers less than 100 nm in diameter, was held on October 27 and 28, 2005, at the Environmental Protection Agency (EPA) Conference Center in Research Triangle Park, North Carolina. The meeting was the eighth in a series of transatlantic conferences first held in Penarth, Wales, at the Medical Research Council Pneumoconiosis Unit (1979), that have fostered long-standing collaborations between researchers in the fields of mineralogy, cell and molecular biology, pathology, toxicology, and environmental/occupational health.

Results: The goal of this meeting, which was largely supported by a conference grant from the NHLBI, was to assemble a group of clinical and basic research scientists who presented and discussed new data on the mechanistic effects of inhaled particulates on the onset and development of morbidity and mortality in the lung and cardiovascular system. Another outcome of the meeting was the elucidation of a number of host susceptibility factors implicated in adverse health effects associated with inhaled pathogenic particulates.

Conclusion: New models and data presented supported the paradigm that both genetic and environmental (and occupational) factors affect disease outcomes from inhaled particulates as well as cardiopulmonary responses. These future studies are encouraged to allow the design of appropriate strategies for prevention and treatment of particulate-associated morbidity and mortality, especially in susceptible populations.

In plain English

This article is a commentary, not an original study. It summarized talks at a scientific symposium held on October 27 and 28, 2005, at the Environmental Protection Agency conference center in Research Triangle Park, North Carolina. The talks covered how inhaled air-pollution particles, silica, asbestos and nanomaterials affect the lungs and heart. The findings it describes come from presenters' laboratory, animal and human studies, many published elsewhere. On asbestos, the article reported several such findings. Iron on amphibole asbestos such as crocidolite and amosite generates reactive oxygen species (damaging forms of oxygen). Chrysotile asbestos transformed a human bronchial cell line into cells that grew in nude mice. Amosite activated the p53 gene. Mice lacking the TNF-alpha receptor resisted chrysotile-induced fibrosis. It also described early work on stripping iron from asbestos using fungi or lichens, which still requires laboratory and animal testing. A further line of work used tiny spheres to deliver a cancer drug to human mesothelioma cells. The authors concluded that the data presented supported the idea that both genetic and environmental, including occupational, factors affect disease from inhaled particles.

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: Commentary / meeting report summarizing presentations at a scientific symposium (not an original study)
• Who was studied: Research presented by clinical and basic scientists at a symposium held October 27 and 28, 2005, at the EPA Conference Center, Research Triangle Park, North Carolina; the underlying studies involved cells, animals and human subjects
• Exposure: Inhaled airborne particulate matter, silica, asbestos (including chrysotile, crocidolite and amosite), metals, cigarette smoke and nanomaterials
• Main results:
  • The article stated, citing earlier work, that active iron ions on amphibole asbestos such as crocidolite or amosite cause sustained generation of reactive oxygen species, which is related to fiber toxicity and to effects on DNA and proteins
  • In work described at the meeting, chrysotile asbestos induced neoplastic transformation in an immortalized human bronchial epithelial cell line, and the transformed cells grew in nude mice; the BigH3 gene was consistently silenced in the tumor cells
  • In work described at the meeting, amosite asbestos activated p53 promoter activity and raised p53 mRNA and protein; in asbestos-instilled rat lungs, p53 expression was blocked by phytic acid, an iron chelator
  • In mouse studies described at the meeting, mice lacking the TNF-alpha receptor were resistant to chrysotile asbestos-induced fibrosis
  • Proposed remediation approaches included bioremediation by soil fungi or lichens that adhere to asbestos fibers and selectively remove iron; the article said the resulting fibers would need in vitro and animal testing
  • In preclinical work presented, acid-prepared mesoporous spheres increased both the delivery and the killing potency of the drug doxorubicin in human mesothelioma cells
• The authors' conclusion: The authors concluded that the new models and data presented supported the view that both genetic and environmental (including occupational) factors affect disease outcomes from inhaled particulates and cardiopulmonary responses
• Limitations the authors state:
  • The synopsis covered only the platform presentations, not the poster presentations at the meeting

Topics

Medical terms in this study, explained in our Lexicon: Pneumoconiosis, Standing, Mineralogy, Pathology.

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