A novel 3D intestine barrier model to study the immune response upon exposure to microplastics
Abstract
The plausibility of human exposure to microplastics has increased within the last years. Microplastics have been found in different food types including seafood, salt, sugar and beverages. So far, human health effects of microplastics after ingestion are unknown. Herein, we designed a novel, three-dimensional in vitro intestinal model consisting of the human intestinal epithelial cell lines Caco-2 and HT29-MTX-E12 as well as human blood monocyte-derived macrophages and dendritic cells that is suitable to assess the possible effects of ingested microplastics. Relevant microplastic particles (in the order of 50-500 µm), including polymers representing tire wear and polyolefins, which represent major sources of microplastic in the EU, were compared to other polymer classes and an inorganic microparticle, healing earth, which is intended for human consumption. Microplastic particles were exposed at concentrations of 823.5-1380.0 µg/cm 2 to the model using a dry powder insufflator system to aerosolize the particles directly on the intestinal model's surface. Cytotoxicity was investigated after 6, 24 and 48 h of exposure via measuring the release of lactate dehydrogenase. Inflammatory end points including the cytokines IL-8, TNFα and IL-1β as well as changes of the barrier integrity after exposure were additionally monitored. We demonstrated that all of the microplastics and the healing earth particles did not cause any significant cytotoxicity or release of (pro-)inflammatory cytokines and did not change the barrier integrity of the co-culture at any of the time points investigated.
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It is unclear if toxicological effects from physical or chemical mechanisms of microplastics are occurring in humans, and at what thresholds effects occur.
“However, it is unclear if toxicological effects from either of these mechanisms are occurring in humans, and at what thresholds effects occur.”
From Microplastics and Anthropogenic Particles in Recreationally Caught Freshwater Fish from an Urbanized Region of the North American Great Lakes (2024) · cites this paper as [69]
There are conflicting reports of no acute toxicity from microplastics.
“there are also conflicting reports of no acute toxicity from microplastics.69,70”
From Microplastics and Anthropogenic Particles in Recreationally Caught Freshwater Fish from an Urbanized Region of the North American Great Lakes (2024) · cites this paper as [69]
Cites
Microplastics as contaminants in the marine environment: A review
Cole, M., Lindeque, P., Halsband, C., & Galloway, T. S. (2011) · Marine Pollution Bulletin · doi:10.1016/j.marpolbul.2011.09.025 · Cited by 6,023 · see citing works
Plastic and Human Health: A Micro Issue?
Wright, S. L., & Kelly, F. J. (2017) · Environmental Science & Technology · doi:10.1021/acs.est.7b00423 · Cited by 3,413 · see citing works
Edmondson, R., Broglie, J. J., Adcock, A. F., & Yang, L. (2014) · ASSAY and Drug Development Technologies · doi:10.1089/adt.2014.573 · Cited by 2,515 · see citing works
Atmospheric transport and deposition of microplastics in a remote mountain catchment
Allen, S., Allen, D., Phoenix, V. R., Roux, G. L., Durantez, P., Simonneau, A., Binet, S., & Galop, D. (2019) · Nature Geoscience · doi:10.1038/s41561-019-0335-5 · Cited by 2,469 · see citing works
Microplastics in bivalves cultured for human consumption
Cauwenberghe, L. V., & Janssen, C. (2014) · Environmental Pollution · doi:10.1016/j.envpol.2014.06.010 · Cited by 2,081 · see citing works
Pinto, M. (1983) · HAL · Cited by 1,752 · see citing works
Airborne microplastics: consequences to human health?
Prata, J. C. (2018) · Environmental Pollution · doi:10.1016/j.envpol.2017.11.043 · Cited by 1,627 · see citing works
Wear and Tear of Tyres: A Stealthy Source of Microplastics in the Environment
Kole, P. J., Löhr, A., Belleghem, F. V., & Ragas, A. M. J. (2017) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph14101265 · Cited by 1,622 · see citing works
Monitoring the abundance of plastic debris in the marine environment
Ryan, P. G., Moore, C. J., van Franeker, J. A., & Moloney, C. L. (2009) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2008.0207 · Cited by 1,565 · see citing works
Rochman, C. M., Tahir, A., Williams, S. L., Baxa, D. V., Lam, R., Miller, J. T., Teh, F., Werorilangi, S., & Teh, S. J. (2015) · Scientific Reports · doi:10.1038/srep14340 · Cited by 1,553 · see citing works
Contributing to marine pollution by washing your face: Microplastics in facial cleansers
Fendall, L. S., & Sewell, M. A. (2009) · Marine Pollution Bulletin · doi:10.1016/j.marpolbul.2009.04.025 · Cited by 1,525 · see citing works
Photodegradation and photostabilization of polymers, especially polystyrene: review
Yousif, E., & Haddad, R. (2013) · SpringerPlus · doi:10.1186/2193-1801-2-398 · Cited by 1,503 · see citing works
Bouwmeester, H., Hollman, P. C. H., & Peters, R. (2015) · Environmental Science & Technology · doi:10.1021/acs.est.5b01090 · Cited by 1,275 · see citing works
Anthropogenic contamination of tap water, beer, and sea salt
Kosuth, M., Mason, S. A., & Wattenberg, E. V. (2018) · PLoS ONE · doi:10.1371/journal.pone.0194970 · Cited by 1,257 · see citing works
Impacts of polystyrene microplastic on the gut barrier, microbiota and metabolism of mice
Jin, Y., Lu, L., Tu, W., Luo, T., & Fu, Z. (2019) · Science of The Total Environment · doi:10.1016/j.scitotenv.2018.08.353 · Cited by 1,100 · see citing works
Synthetic Polymer Contamination in Bottled Water
Mason, S. A., Welch, V. G., & Neratko, J. (2018) · Frontiers in Chemistry · doi:10.3389/fchem.2018.00407 · Cited by 1,100 · see citing works
Three-Dimensional Cell Culture Matrices: State of the Art
Lee, J., Cuddihy, M. J., & Kotov, N. A. (2008) · Tissue Engineering Part B: Reviews · doi:10.1089/teb.2007.0150 · Cited by 1,047 · see citing works
Microplastics in commercial bivalves from China
Li, J., Yang, D., Li, L., Jabeen, K., & Shi, H. (2015) · Environmental Pollution · doi:10.1016/j.envpol.2015.09.018 · Cited by 1,025 · see citing works
Microfold (M) cells: important immunosurveillance posts in the intestinal epithelium
Mabbott, N. A., Donaldson, D. S., Ohno, H., Williams, I. R., & Mahajan, A. (2013) · Mucosal Immunology · doi:10.1038/mi.2013.30 · Cited by 721 · see citing works
Microplastics pollution in different aquatic environments and biota: A review of recent studies
Rezania, S., Park, J., Din, M. F. M., Taib, S. M., Talaiekhozani, A., Yadav, K. K., & Kamyab, H. (2018) · Marine Pollution Bulletin · doi:10.1016/j.marpolbul.2018.05.022 · Cited by 679 · see citing works
Non-pollen particulates in honey and sugar
Liebezeit, G., & Liebezeit, E. (2013) · Food Additives & Contaminants Part A · doi:10.1080/19440049.2013.843025 · Cited by 612 · see citing works
Synthetic particles as contaminants in German beers
Liebezeit, G., & Liebezeit, E. (2014) · Food Additives & Contaminants Part A · doi:10.1080/19440049.2014.945099 · Cited by 558 · see citing works
Microplastics in Spanish Table Salt
Iñiguez, M. E., Conesa, J. A., & Fullana, A. (2017) · Scientific Reports · doi:10.1038/s41598-017-09128-x · Cited by 419 · see citing works
Oral exposure to polystyrene nanoparticles affects iron absorption
Mahler, G. J., Esch, M. B., Tako, E., Southard, T. L., Archer, S. D., Glahn, R. P., & Shuler, M. L. (2012) · Nature Nanotechnology · doi:10.1038/nnano.2012.3 · Cited by 339 · see citing works
Microplastics pollution and reduction strategies
Wu, W., Yang, J., & Criddle, C. S. (2016) · Frontiers of Environmental Science & Engineering · doi:10.1007/s11783-017-0897-7 · Cited by 334 · see citing works
Probiotics up-regulate MUC-2 mucin gene expression in a Caco-2 cell-culture model
Mattar, A., Teitelbaum, D. H., Drongowski, R. A., Fan, Y., Harmon, C. M., & Coran, A. G. (2002) · Pediatric Surgery International · doi:10.1007/s00383-002-0855-7 · Cited by 309 · see citing works
Walter, E., Janich, S. L., Roessler, B. J., Hilfinger, J. M., & Amidon, G. L. (1996) · Journal of Pharmaceutical Sciences · doi:10.1021/js960110x · Cited by 272 · see citing works
Antunes, F., Andrade, F., Araújo, F., Ferreira, D., & Sarmento, B. F. C. C. (2012) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2012.10.003 · Cited by 270 · see citing works
Environmental biodegradation of synthetic polymers II. Biodegradation of different polymer groups
Eubeler, J. P., Bernhard, M., & Knepper, T. P. (2010) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2009.09.005 · Cited by 259 · see citing works
Béduneau, A., Tempesta, C., Fimbel, S., Pellequer, Y., Jannin, V., Demarne, F., & Lamprecht, A. (2014) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2014.03.017 · Cited by 227 · see citing works
Leonard, F., Collnot, E.-M., & Lehr, C. (2010) · Molecular Pharmaceutics · doi:10.1021/mp1000795 · Cited by 221 · see citing works
Molecular description of a 3D in vitro model for the study of epithelial ovarian cancer (EOC)
Zietarska, M., Maugard, C. M., Filali‐Mouhim, A., Alam‐Fahmy, M., Tonin, P. N., Provencher, D. M., & Mes‐Masson, A. (2007) · Molecular Carcinogenesis · doi:10.1002/mc.20315 · Cited by 209 · see citing works
Araújo, F., & Sarmento, B. F. C. C. (2013) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2013.10.003 · Cited by 195 · see citing works
Kämpfer, A. A. M., Urbán, P., Gioria, S., Kanase, N., Stone, V., & Kinsner‐Ovaskainen, A. (2017) · Toxicology in Vitro · doi:10.1016/j.tiv.2017.08.011 · Cited by 177 · see citing works
Schimpel, C., Teubl, B. J., Absenger, M., Meindl, C., Fröhlich, E., Leitinger, G., Zimmer, A., & Roblegg, E. (2014) · Molecular Pharmaceutics · doi:10.1021/mp400507g · Cited by 172 · see citing works
Rimoldi, M., Chieppa, M., Larghi, P., Vulcano, M., Allavena, P., & Rescigno, M. (2005) · Blood · doi:10.1182/blood-2004-11-4321 · Cited by 159 · see citing works
Navabi, N., McGuckin, M. A., & Lindén, S. K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068761 · Cited by 157 · see citing works
Rescigno, M., & Borrow, P. (2001) · Cell · doi:10.1016/s0092-8674(01)00454-8 · Cited by 134 · see citing works
Lehmann, A. D., Schneider‐Daum, N., Bur, M., Lehr, C., Gehr, P., & Rothen‐Rutishauser, B. (2010) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2010.10.014 · Cited by 134 · see citing works
Self-citationSusewind, J., Carvalho‐Wodarz, C. D. S., Repnik, U., Collnot, E.-M., Schneider‐Daum, N., Griffiths, G. W., & Lehr, C. (2015) · Nanotoxicology · doi:10.3109/17435390.2015.1008065 · Cited by 112 · see citing works
SMALL INTESTINE TRANSIT TIME IN THE NORMAL SMALL BOWEL STUDY
KIM, S. K. (1968) · American Journal of Roentgenology · doi:10.2214/ajr.104.3.522 · Cited by 101 · see citing works
Hallab, N., McAllister, K., Brady, M. F., & Jarman-Smith, M. (2012) · Journal of Biomedical Materials Research. Part B - Applied biomaterials · doi:10.1002/jbm.b.31974 · Cited by 71 · see citing works
Meeting the Needs for Released Nanomaterials Required for Further Testing—The SUN Approach
Nowack, B., Boldrin, A., Caballero-Guzman, A., Hansen, S. F., Gottschalk, F., Heggelund, L. R., Hennig, M., Mackevica, A., Maes, H. M., Navrátilová, J., et al. (2016) · Environmental Science & Technology · doi:10.1021/acs.est.5b04472 · Cited by 65 · see citing works
Self-citationNeubauer, N., Scifo, L., Navrátilová, J., et al. (2017) · Environmental Science & Technology · doi:10.1021/acs.est.7b02578 · Cited by 58 · see citing works
Calatayud, M., Vázquez, M., Devesa, V., et al. (2012) · Chemical Research in Toxicology · doi:10.1021/tx300295n · Cited by 55 · see citing works
Wohlleben, W., Meyer, J., Muller, J. M., et al. (2016) · Environmental Science Nano · doi:10.1039/c6en00094k · Cited by 47 · see citing works
Self-citationAmorim, M. J. B., Lin, S., Schlich, K., Navas, J. M., Brunelli, A., Neubauer, N., Vilsmeier, K., Costa, A. L., Gondikas, A. P., Xia, T., et al. (2018) · Environmental Science & Technology · doi:10.1021/acs.est.7b04122 · Cited by 45 · see citing works
Self-citationPolyethylene wear debris in modular acetabular prostheses.
Pc, C., Eh, M., Pinto, J. G., et al. (1995) · PubMed · Cited by 44 · see citing works
Absorption of Orally Administered Enzymes
Gardner, M. L. G., & Steffens, K. (1995) · Springer eBooks · doi:10.1007/978-3-642-79511-4 · Cited by 34 · see citing works
Nanomaterials to microplastics: Swings and roundabouts
Scott-Fordsmand, J. J., Navas, J. M., Hund‐Rinke, K., et al. (2017) · Nano Today · doi:10.1016/j.nantod.2017.09.002 · Cited by 25 · see citing works
Persorption — Criticism and Agreement as Based upon In Vitro and In Vivo Studies on Mammals
Steffens, K. ‐. (1995) · Springer eBooks · doi:10.1007/978-3-642-79511-4_2 · Cited by 18 · see citing works
Taillefer (2000) · doi:10.1002/(sici)1520-6017(200001)89:1
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Danopoulos, E., Twiddy, M., West, R., & Rotchell, J. M. (2022) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2021.127861 · Cited by 230 · see citing works
Milne, M. H., Helm, P. A., Munno, K., Bhavsar, S. P., & Rochman, C. M. (2024) · Environmental Health Perspectives · doi:10.1289/ehp13540 · Cited by 15 · see citing works
“69,70 Discrepancies are likely due to exposure experiments using di ff erent concentrations, but also these variations in results could be relevant to the polymer type, morphology, or size used in the study.”
- Authors
- Lehner, R., Wohlleben, W., Septiadi, D., Landsiedel, R., Petri-Fink, A., & Rothen-Rutishauser, B.
- Affiliations
- University of Fribourg (CH)
- BASF (Germany) (DE)
- Corresponding author
- Lehner, Roman
- Venue
- Archives of Toxicology
- Published
- 2020-04-19
- Volume
- 94
- Issue
- 7
- Pages
- 2463-2479
- ISSN
- 0340-5761 (ISSN-L)
- 1432-0738
- OpenAlex
- W3016771629
- Cited by
- 123
- References
- 52
- Citations by year
- 2026: 11 · 2025: 25 · 2024: 24 · 2023: 23 · 2022: 20 · 2021: 12 · 2020: 7 · 2013: 1
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Toxicology (publishedVersion)
- PubMed (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- Funders
- Adolphe Merkle Foundation
- BASF
- Topics
- Physical Sciences › Environmental Science › Pollution › Microplastics and Plastic Pollution
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Physical Sciences › Environmental Science › Pollution › Pharmaceutical and Antibiotic Environmental Impacts
- Keywords
- microplastics, intestinal barrier, Caco-2 cells, macrophages, dendritic cells, cytotoxicity, inflammatory cytokines, barrier integrity, polyolefins, tire wear particles, aerosols
- MeSH terms
- Microplastics, Aerosols, Cell Survival, Dendritic Cells, Humans, Intestinal Mucosa, Macrophages, Particle Size, Permeability, Time Factors, Cytokines, Electric Impedance, Risk Assessment, Inflammation Mediators, Coculture Techniques, Caco-2 Cells, HT29 Cells
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