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In Vitro Alveolar Epithelial Models Toward the Prediction of Toxicity and Translocation of Nanoparticles: A Complementary Method for Mechanism Analyses in Humans

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Part of the Current Topics in Environmental Health and Preventive Medicine book series (CTEHPM)

Abstract

Nanoparticles are promising materials in research and industrial fields because of their unique characteristics, their safety and toxicity are still being investigated. Although the safety and toxicity of nanomaterials are predicted by animal experiments, obtained results may be inconsistent with human outcomes due to the species difference. Recently, there has been an increasing interest in in vitro lung models, which allow control of experimental parameters and quantitative analyses, for the prediction of lung injuries and translocation into secondary organs of nanoparticles. In this section, we focus on developing in vitro alveolar models consisting of not only human-derived cell lines but also primary rat cells as complementary methods for intratracheal instillation in rats. We also coculture with macrophages to approach physiologically relevant alveolar environment. In addition, cytotoxicity and permeability tests of nanoparticles are presented to evaluate the in vitro alveolar coculture modles developed here. To further improve the physiological relevance of in vitro alveolar models, we discuss future issues.

Keywords

In vitro lung model Nanoparticles Pulmonary cytotoxicity Pulmonary permeability Alveolar type I and II cells Alveolar macrophage 

Notes

Acknowledgements

The works shown here are collaborative work with Mr. Takuya Aoyama, Mr. Kodai Harano, Ms. Xinying Xu, and Ms. Ayaka Uemura. This work is part of the research program “Development of innovative methodology for safety assessment of industrial nanomaterials” supported by the Ministry of Economy, Trade and Industry (METI) of Japan.

References

  1. 1.
    Nel A, Xia T, Mädler L, Li N. Toxic potential of materials at the nano level. Science. 2006;311:622–7.CrossRefGoogle Scholar
  2. 2.
    De Jong WH, Borm PJA. Drug delivery and nanoparticles: applications and hazards. Int J Med. 2008;3:133–49.Google Scholar
  3. 3.
    Sung JC, Pulliam BL, Edwards DA. Nanoparticles for drug delivery to the lungs. Trends Biotechnol. 2007;25:563–70.CrossRefGoogle Scholar
  4. 4.
    Klein CL, Wiench K, Wiemann M, Ma-Hock L, van Ravenzwaay B, Landsiedel R. Hazard identification of inhaled nanomaterials: making use of short-term inhalation studies. Arch Toxicol. 2012;86:1137–51.CrossRefGoogle Scholar
  5. 5.
    Sayes CM, Reed KL, Warheit DB. Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. Toxicol Sci. 2007;97:163–80.CrossRefGoogle Scholar
  6. 6.
    Yacobi NR, Phuleria HC, Demaio L, Liang CH, Peng CA, Sioutas C, Borok Z, Kim KJ, Crandall ED. Nanoparticle effects on rat alveolar epithelial cell monolayer barrier properties. Toxicol In Vitro. 2007;21:1373–81.CrossRefGoogle Scholar
  7. 7.
    Trouiller B, Reliene R, Westbrook A, Solaimani P, Schiestl RH. Titanium dioxide nanoparticles induce DNA damage and genetic instability in vivo in mice. Cancer Res. 2009;69:8784–9.CrossRefGoogle Scholar
  8. 8.
    Gurr JR, Wang ASS, Chen CH, Jan KY. Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. Toxicology. 2005;213:66–73.CrossRefGoogle Scholar
  9. 9.
    Kim IS, Baek M, Choi SJ. Comparative cytotoxicity of Al2O3, CeO2, TiO2 and ZnO nanoparticles to human lung cells. J Nanosci Nanotechnol. 2010;10:3453–8.CrossRefGoogle Scholar
  10. 10.
    Lai JCK, Lai MB, Jandhyam S, Dukhande VV, Bhushan A, Daniels CK, Leung SW. Exposure to titanium dioxide and other metallic oxide nanoparticles induces cytotoxicity on human neural cells and fibroblasts. Int J Nanomedicine. 2008;3:533–45.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Lin W, Huang YW, Zhou XD, Ma Y. In vitro toxicity of silica nanoparticles in human lung cancer cells. Toxicol Appl Pharmacol. 2006;217:252–9.CrossRefGoogle Scholar
  12. 12.
    Mahmoudi M, Lynch I, Ejtehadi MR, Monopoli MP, Bombelli FB, Laurent S. Protein-nanoparticle interactions: opportunities and challenges. Chem Rev. 2011;111:5610–37.CrossRefGoogle Scholar
  13. 13.
    Lieber M, Smith B, Szakal A, Nelson-Rees W, Todaro G. A continuous tumor-cell line from a human lung carcinoma with properties of type II alveolar epithelial cells. Int J Cancer. 1976;17:62–70.CrossRefGoogle Scholar
  14. 14.
    Foster KA, Oster CG, Mayer MM, Avery ML, Audus KL. Characterization of the A549 cell line as a type II pulmonary epithelial cell model for drug metabolism. Exp Cell Res. 1998;243:359–66.CrossRefGoogle Scholar
  15. 15.
    Daigneault M, Preston JA, Marriott HM, Whyte KB, Dockrell DH. The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages. PLoS One. 2010;5:e8668.CrossRefGoogle Scholar
  16. 16.
    Fleit HB, Kobasiuk CD. The human monocyte-like cell line THP-1 expresses FcγRI and FcγRII. J Leukoc Biol. 1991;49:556–65.CrossRefGoogle Scholar
  17. 17.
    Braakhuis HM, Kloet SK, Kezic S, Kuper F, Park MVDZ, Bellmann S, van der Zande M, Gac SL, Krystek P, Peters RB, Rietjents IMCM, Bouwmeester H. Progress and future of in vitro models to study translocation of nanoparticles. Arch Toxicol. 2015;89:1469–95.CrossRefGoogle Scholar
  18. 18.
    Dobbs LG, Mason RJ. Pulmonary alveolar type II cells isolated from rats. J Clin Invest. 1979;63:378–87.CrossRefGoogle Scholar
  19. 19.
    Sakagami M. In vivo, in vitro and ex vivo models to assess pulmonary absorption and disposition of inhaled therapeutics for systemic delivery. Adv Drug Deliv Rev. 2006;58:1030–60.CrossRefGoogle Scholar
  20. 20.
    Wallace WAH, Gillooly M, Lamb D. Intra-alveolar macrophage numbers in current smokers and non-smokers: a morphometric study of tissue sections. Thorax. 1992;47:437–40.CrossRefGoogle Scholar
  21. 21.
    Iwasawa K, Tanaka G, Aoyama T, Chowdhury MM, Komori K, Tanaka-Kagawa T, Jinno H, Sakai Y. Prediction of phthalate permeation through pulmonary alveoli using a cultured A549 cell-based in vitro alveolus model and a numerical simulation. AATEX. 2013;18:19–31.Google Scholar
  22. 22.
    Komori K, Murai K, Miyajima S, Fujii T, Mohri S, Ono Y, Sakai Y. Deveopment of an in vitro batch-type closed gas exposure device with an alveolar epithelial cell line, A549, for toxicity evaluations of gaseous compounds. Anal Sci. 2008;24:957–62.CrossRefGoogle Scholar
  23. 23.
    Whitcutt MJ, Adler KB, Wu R. A biphasic chamber system for maintaining polarity of differentiation of cultured respiratory tract epithelial cells. In Vitro Cell Dev Biol. 1988;24:420–8.CrossRefGoogle Scholar
  24. 24.
    Sakai Y, Tomita K, Suzuki M, Ono Y, Sakoda A. Development of a toxicity evaluation system for gaseous compounds using air-liquid interface culture of a human bronchial epithelial cell line. Calu-3 AATEX. 2005;11:59–67.Google Scholar
  25. 25.
    Weibel ER. Morphometry of the human lung: the state of the art after two decades. Bull Eur Physiopathol Respir. 1979;15:999–1013.PubMedGoogle Scholar
  26. 26.
    Dobbs LG, Pian MS, Magrio M, Dumars S, Allen L. Maintenance of the differentiated type II cell phenotype by culture with an apical air surface. Am J Physiol. 1997;273:L347–54.CrossRefGoogle Scholar
  27. 27.
    Huh D, Matthews BD, Mammoto A, Montoya-Zavala H, Hsin Y, Ingber DE. Reconstituting organ-level lung functions on a chip. Science. 2010;328:1662–8.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Chemical System EngineeringThe University of TokyoTokyoJapan
  2. 2.Institute of Industrial ScienceThe University of TokyoTokyoJapan
  3. 3.Department of Laboratory MedicineIwate Medical University School of MedicineMoriokaJapan

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