Fibrous nanocellulose, crystalline nanocellulose, carbon nanotubes, and crocidolite asbestos elicit disparate immune responses upon pharyngeal aspiration in mice

Our plain-English summary of Fibrous nanocellulose, crystalline nanocellulose, carbon nanotubes, and crocidolite asbestos elicit disparate immune responses upon pharyngeal aspiration in mice, by E.J. Park, T.O. Khaliullin, M.R. Shurin, et al (Journal of Immunotoxicology, 2018).

The study

• Authors: E.J. Park, T.O. Khaliullin, M.R. Shurin, E.R. Kisin, N. Yanamala, B. Fadeel, J. Chang, A.A. Shvedova
• Journal: Journal of Immunotoxicology
• Published: 2018;15(1):12-23
• Cited by: 41 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

With the rapid development of synthetic alternatives to mineral fibers, their possible effects on the environment and human health have become recognized as important issues worldwide. This study investigated effects of four fibrous materials, i.e. nanofibrillar/nanocrystalline celluloses (NCF and CNC), single-walled carbon nanotubes (CNTs), and crocidolite asbestos (ASB), on pulmonary inflammation and immune responses found in the lungs, as well as the effects on spleen and peripheral blood immune cell subsets. BALB/c mice were given NCF, CNC, CNT, and ASB on Day 1 by oropharyngeal aspiration. At 14 days post-exposure, the animals were evaluated. Total cell number, mononuclear phagocytes, polymorphonuclear leukocytes, lymphocytes, and LDH levels were significantly increased in ASB and CNT-exposed mice. Expression of cytokines and chemokines in bronchoalveolar lavage (BAL) was quite different in mice exposed to four particle types, as well as expression of antigen presentation-related surface proteins on BAL cells. The results revealed that pulmonary exposure to fibrous materials led to discrete local immune cell polarization patterns with a TH2-like response caused by ASB and TH1-like immune reaction to NCF, while CNT and CNC caused non-classical or non-uniform responses. These alterations in immune response following pulmonary exposure should be taken into account when testing the applicability of new nanosized materials with fibrous morphology.

In plain English

This was an animal experiment. Female BALB/c mice each received a single dose, aspirated into the lungs from the throat, of one of four materials: UICC standard crocidolite asbestos, single-walled carbon nanotubes, or crystalline or fibrillar nanocellulose (two dose levels each). Control mice received saline. The mice were examined 14 days later. All four materials were still in the lungs, and only the asbestos could not be completely engulfed by immune cells. Cell counts in lung washings rose significantly after asbestos, after nanotubes and after the higher nanocellulose doses, most in asbestos-exposed mice (up to four-fold). Total protein in the washings rose significantly only after asbestos (1.4-fold versus controls). Only asbestos significantly raised the percentage of eosinophils in the blood. Asbestos caused the most marked cytokine changes, including increases in IL-4, IL-5 and IL-6. The authors concluded that asbestos induced a much stronger response, pointing to a possible TH2-type pattern, while fibrillar nanocellulose produced a TH1-like response. In their view, neither nanocellulose nor the nanotubes studied behaved like asbestos. They cautioned that the study used a single timepoint and bolus exposures.

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 experiment (mice given test materials by pharyngeal aspiration, compared with saline controls)
• Who was studied: Specific pathogen-free female BALB/c mice, 7 to 8 weeks old, from Jackson Laboratories, in seven groups; procedures approved by the NIOSH animal care committee
• Exposure: A single pharyngeal aspiration of UICC standard crocidolite asbestos, acid-treated single-walled carbon nanotubes, crystalline nanocellulose (CNC) or fibrillar nanocellulose (NCF), or saline for controls. Asbestos and nanotubes were given at one dose, printed in this copy as '40 mg/mouse'. CNC and NCF were given at two doses, printed as 40 and 80 'mg' per mouse. Mice were evaluated 14 days after exposure.
• Main results:
  • All four materials remained in the lungs at 14 days. Only asbestos could not be completely engulfed by phagocytes.
  • Total cell and mononuclear phagocyte numbers in lung lavage rose significantly in the asbestos and nanotube groups and in the higher-dose CNC and NCF groups. The increase was highest in asbestos-treated mice, up to four-fold.
  • Total protein in lavage fluid rose significantly only in asbestos-treated mice (1.4-fold versus control, p less than 0.05).
  • LDH activity (a marker of damage) rose significantly in asbestos-treated mice (140 U/l) and in the lower-dose CNC and nanotube groups (102 and 98 U/l), each p less than 0.05 versus control.
  • Asbestos-exposed mice had the most marked cytokine and chemokine changes in lavage fluid. These included increases in IL-4, IL-5 and IL-6 and decreases in IL-3, IL-9, IL-12p70 and IL-17a.
  • In cluster analysis of cytokines, the asbestos sample was far from all other treatments. NCF clustered with nanotubes, and CNC grouped with controls.
  • Only asbestos exposure significantly raised the percentage of eosinophils in the blood compared with controls.
  • In the spleen, the T-cell composition shifted toward CD8 T-cells in asbestos- and nanotube-treated mice compared with controls.
• The authors' conclusion: The authors concluded that crocidolite asbestos produced a much stronger and distinct immune response, indicative of chronic inflammation and possible TH2-type polarization, while fibrillar nanocellulose produced a TH1-like response. They also concluded that the nanocellulose agents and the single-walled carbon nanotubes studied did not behave as 'asbestos-like' materials.
• Limitations the authors state:
  • Only a single timepoint was studied and bolus exposures were used, so conclusions should be generalized with care.
  • Bolus pharyngeal aspiration may not fully represent inhalation exposure in humans.
  • Immune cell migration in response to fiber persistence in the lungs was not evaluated.

Topics

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

Medical terms in this study, explained in our Lexicon: Crystalline, Crocidolite, Mineral Fiber, Inflammation, Cytokine, Bronchoalveolar Lavage (BAL).

Related studies

• Comparative proteomics and pulmonary toxicity of instilled single-walled carbon nanotubes, crocidolite asbestos, and ultrafine carbon black in mice — J.G. Teeguarden, B.J. Webb-Robertson, et al. (2011)
• Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos — A.R. Murray, E.R. Kisin, et al. (2012)
• Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study — B.N. Snyder-Talkington, C. Dong, et al. (2016)
• Inhalation and Oropharyngeal Aspiration Exposure to Rod-Like Carbon Nanotubes Induce Similar Airway Inflammation and Biological Responses in Mouse Lungs — P. Kinaret, M. Ilves, et al. (2017)
• Carbon Nanotube and Asbestos Exposures Induce Overlapping but Distinct Profiles of Lung Pathology in Non-Swiss Albino CF-1 Mice — E.A. Frank, V.S. Carreira, et al. (2016)
• A Single Aspiration of Rod-like Carbon Nanotubes Induces Asbestos-like Pulmonary Inflammation Mediated in Part by the IL-1 Receptor — E.M. Rydman, M. Ilves, et al. (2015)

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