Differential Responses of Murine Alveolar Macrophages to Elongated Mineral Particles of Asbestiform Versus Non-Asbestiform Varieties

Details

• Personal Author:
  Khaliullin TO ; Kisin ER ; Shvedova AA ; Yanamala N
• Description:
  Occupational exposures to asbestiform elongated mineral particles (EMP) may lead to diffuse fibrosis, lung cancer, malignant mesothelioma and autoimmune diseases. Cleavage fragments (CF) are chemically identical to asbestiform varieties of mineral, but there is no consensus on whether to treat them as asbestos from the toxicological and regulatory standpoint. Alveolar macrophages (AM) are the first-responders to inhaled particulates, participating in clearance and activating the other resident and recruited immunocompetent cells, which has an impact on the long-term outcomes. In the current study we are addressing the question of how differences in EMP crystal growth habit (asbestiform vs. non-asbestiform) affect AM responses. MPI cells, a non-transformed line that closely mimics AM phenotype, were treated with mass-, surface area- (s.a.), and particle number- (p.n.) equivalent doses of respirable asbestiform and non-asbestiform riebeckite/tremolite EMP (median lengths 4.5-5.5 microm) for 24 h with or without LPS (5 ng/ml). We assessed viability and apoptotic response, lactate dehydrogenase (LDH) and cytokines in cell supernatants. Riebeckite/tremolite asbestos and CF were taken up and induced similar LDH leakage and decrease in viability at the s.a. equivalent doses. At the equal mass, asbestiform EMPs were clearly more cytotoxic. When treated with equal p.n., CF had more pronounced cytotoxic effects. Apoptosis induction was more pronounced in asbestos-treated cells, compared to CF in all comparisons (mass/s.a./p.n.). There was an increase in chemokines and elevated pro-inflammatory cytokine secretion compared to control. Principal component analysis of the cytokine/chemokine secretion showed close clustering for the s.a. and p.n. equivalent treatments. LPS stimulation shifted the cytokine profiles towards inflammation compared to non-LPS-stimulated cells, with more IL-1beta and TNF-alpha secretion in asbestos-treated cells compared to CF. In conclusion, murine AM initial responses to respirable EMP of similar lengths, but different growth habit depend on the s.a. metric rather than the mass or the p.n. The study also confirms that asbestiform habit itself is an important determinant of some signaling pathways, i.e. apoptosis. Finding out what metric is critical for the mineral fiber toxicity is a complex task and the in vivo study with the same EMP is underway to further address the issue. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Asbestos Blood Cytotoxins Fibrosis Hazardous Substances Immune System Inorganic Chemicals Laboratories Lung Lung Diseases Macrophages Minerals Neoplasms Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Airborne Particles Alveolar Cells Asbestos Fibers Cell Signaling Cellular Effects Cellular Uptake Cytokines Cytotoxic Effects Cytotoxicity Dose Response Exposure Assessment Fibers Immune Reaction Immune System Laboratory Animals Laboratory Testing Lung Cancer Lung Cells Lung Disease Lung Fibrosis Pulmonary Effects Signaling Pathways Surface Properties Toxic Effects Toxic Materials

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  39
• Volume:
  174
• Issue:
  1
• NIOSHTIC Number:
  nn:20058849
• Citation:
  Toxicologist 2020 Mar; 174(1):39
• CAS Registry Number:
  Asbestos (CAS RN 1332-21-4) ; Tremolite (Ca2[(Mg0.9-1Fe0-0.1)4.5-5Al0-0.5](Si7.5-8Al0-0.5)(OH)2O22) (CAS RN 14567-73-8)
• Federal Fiscal Year:
  2020
• NORA Priority Area:
  Mining
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 59th Annual Meeting and ToxExpo, March 15-19, 2020, Anaheim, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:60449feba544d794630099231a9b0ea3698d84b081a7b3c90e067b206b2e00a3b574e0b4aa9c24a91b81e5f827f91b6ba397fa448376301b6019b53468185d41
• Download URL:
  https://stacks.cdc.gov/view/cdc/223234/cdc_223234_DS1.pdf
• File Type:
  [PDF - 524.52 KB ]