DOI QR코드

DOI QR Code

Dysregulation of Cellular Immune Functions on Gastric Administration to Mixtures of Polyethlene Microplastics and Metallic Lead in Mice

폴리에틸렌 미세플라스틱과 납의 복합노출에 따른 실험동물의 세포면역기능 조절 장애 평가

  • Gyoungwoo Lee (Department of Toxicity Assessment, Graduate School of Medical and Health Industry, Daegu Catholic University) ;
  • Changyul Kim (Department of Toxicity Assessment, Graduate School of Medical and Health Industry, Daegu Catholic University)
  • 이경우 (대구가톨릭대학교 의료보건산업대학원 화학물질독성평가학과) ;
  • 김창열 (대구가톨릭대학교 의료보건산업대학원 화학물질독성평가학과)
  • Received : 2023.02.07
  • Accepted : 2023.02.15
  • Published : 2023.02.28

Abstract

Background: The existing research results on the combined toxicity of these pollutants using mammals, such as rodents, are insufficient, especially in relation to changes in the immune system. Objectives: This study aims at evaluating the cellular immune response to PE-MPs solely or when combined with Pb, which possess excellent adsorption capacity with PE-MPs and is commonly co-exposed in our daily lives. Methods: The study investigated the cellular immune function of 9-week ICR mice with 28 days exposure to PE-MPs (2 mg/mouse/day) and Pb (0.1 mM in distilled water) individually and in combination. PE-MPs were administered via gastric intubation while the lead intake was conducted via the oral drinking water route. Cellular immunity was evaluated by analyzing the production for TH1 cytokines namely, TNF-α and IFN-𝛾 and TH2 cytokines, IL-4 and IL-6 in culture supernatants from polyclonally activated splenic mononuclear cells ex vivo. Results: Both the PE-MPs only and the PE-MPs+Pb exposure group revealed an increased TH1 response with elevated TNF-α and IFN-𝛾 levels and downregulated TH2 response with low IL-4, and IL-6 production levels compared to the control group. Furthermore, an increased IFN-𝛾/IL-4 ratio was found in the PE-MPs only and PE-MPs+Pb exposure groups, which indicated the skewedness to TH1 response. Meanwhile, reduced blood hemoglobin levels and increased levels of IL-4, the dominant TH2 cytokine in the Pb-only exposure group, were observed. Conclusions: Our current findings on the predominance of TH1 immune response in the PE-MPs and PE-MPs+Pb groups suggest that PE-MPs could be responsible for the predominant induction of the cellular immune changes. This finding could be used as an important landmark in research related to TH1 predominance, such as autoimmune diseases. It suggests that additional research on immune modulation using longer exposure durations or the same exposure route is required to elucidate stronger findings.

Keywords

Acknowledgement

본 연구는 한국화학물질관리협회 화학물질 안전관리 전문 인력 양성 사업의 지원을 받아 수행되었음.

References

  1. Gaulton T, Hague C, Cole D, Thomas E, Duarte-Davidson R. Global event-based surveillance of chemical incidents. J Expo Sci Environ Epidemiol. 2023; 33(1): 111-117. https://doi.org/10.1038/s41370-021-00384-8
  2. Doyle MJ, Watson W, Bowlin NM, Sheavly SB. Plastic particles in coastal pelagic ecosystems of the Northeast Pacific ocean. Mar Environ Res. 2011; 71(1): 41-52. https://doi.org/10.1016/j.marenvres.2010.10.001
  3. Galafassi S, Nizzetto L, Volta P. Plastic sources: a survey across scientific and grey literature for their inventory and relative contribution to microplastics pollution in natural environments, with an emphasis on surface water. Sci Total Environ. 2019; 693: 133499.
  4. Turroni S, Wright S, Rampelli S, Brigidi P, Zinzani PL, Candela M. Microplastics shape the ecology of the human gastrointestinal intestinal tract. Curr Opin Toxicol. 2021; 28: 32-37. https://doi.org/10.1016/j.cotox.2021.09.006
  5. Schirinzi GF, Perez-Pomeda I, Sanchis J, Rossini C, Farre M, Barcelo D. Cytotoxic effects of commonly used nanomaterials and microplastics on cerebral and epithelial human cells. Environ Res. 2017; 159: 579-587. https://doi.org/10.1016/j.envres.2017.08.043
  6. Wright SL, Kelly FJ. Plastic and human health: a micro issue? Environ Sci Technol. 2017; 51(12): 6634-6647. https://doi.org/10.1021/acs.est.7b00423
  7. Tong X, Li B, Li J, Li L, Zhang R, Du Y, et al. Polyethylene microplastics cooperate with Helicobacter pylori to promote gastric injury and inflammation in mice. Chemosphere. 2022; 288(Pt 2): 132579.
  8. Song YM, Kim CY. Toxicities demonstrated in dams and neonates following intragastric intubation of polyethylene microplastics to pregnant mice. J Environ Health Sci. 2021; 47(5): 446-453. https://doi.org/10.5668/JEHS.2021.47.5.446
  9. Deng Y, Zhang Y, Lemos B, Ren H. Tissue accumulation of microplastics in mice and biomarker responses suggest widespread health risks of exposure. Sci Rep. 2017; 7: 46687.
  10. Barboza LGA, Vieira LR, Branco V, Carvalho C, Guilhermino L. Microplastics increase mercury bioconcentration in gills and bioaccumulation in the liver, and cause oxidative stress and damage in Dicentrarchus labrax juveniles. Sci Rep. 2018; 8: 15655.
  11. Wen B, Jin SR, Chen ZZ, Gao JZ, Liu YN, Liu JH, et al. Single and combined effects of microplastics and cadmium on the cadmium accumulation, antioxidant defence and innate immunity of the discus fish (Symphysodon aequifasciatus). Environ Pollut. 2018; 243(Pt A): 462-471. https://doi.org/10.1016/j.envpol.2018.09.029
  12. Yang Z, Zhu L, Liu J, Cheng Y, Waiho K, Chen A, et al. Polystyrene microplastics increase Pb bioaccumulation and health damage in the Chinese mitten crab Eriocheir sinensis. Sci Total Environ. 2022; 829: 154586.
  13. Gao F, Li J, Sun C, Zhang L, Jiang F, Cao W, et al. Study on the capability and characteristics of heavy metals enriched on microplastics in marine environment. Mar Pollut Bull. 2019; 144: 61-67. https://doi.org/10.1016/j.marpolbul.2019.04.039
  14. Zhou Y, Yang Y, Liu G, He G, Liu W. Adsorption mechanism of cadmium on microplastics and their desorption behavior in sediment and gut environments: the roles of water pH, lead ions, natural organic matter and phenanthrene. Water Res. 2020; 184: 116209.
  15. Holmes LA, Turner A, Thompson RC. Interactions between trace metals and plastic production pellets under estuarine conditions. Mar Chem. 2014; 167: 25-32. https://doi.org/10.1016/j.marchem.2014.06.001
  16. Barus BS, Chen K, Cai M, Li R, Chen H, Li C, et al. Heavy metal adsorption and release on polystyrene particles at various salinities. Front Mar Sci. 2021; 8: 671802.
  17. Wani AL, Ara A, Usmani JA. Lead toxicity: a review. Interdiscip Toxicol. 2015; 8(2): 55-64. https://doi.org/10.1515/intox-2015-0009
  18. Caito S, Aschner M. Developmental neurotoxicity of lead. Adv Neurobiol. 2017; 18: 3-12. https://doi.org/10.1007/978-3-319-60189-2_1
  19. Hauptman M, Bruccoleri R, Woolf AD. An update on childhood lead poisoning. Clin Pediatr Emerg Med. 2017; 18(3): 181-192. https://doi.org/10.1016/j.cpem.2017.07.010
  20. Santa Maria MP, Hill BD, Kline J. Lead (Pb) neurotoxicology and cognition. Appl Neuropsychol Child. 2019; 8(3): 272-293. https://doi.org/10.1080/21622965.2018.1428803
  21. Sokol RZ, Berman N. The effect of age of exposure on lead-induced testicular toxicity. Toxicology. 1991; 69(3): 269-278. https://doi.org/10.1016/0300-483X(91)90186-5
  22. Matovic V, Buha A, Dukic-Cosic D, Bulat Z. Insight into the oxidative stress induced by lead and/or cadmium in blood, liver and kidneys. Food Chem Toxicol. 2015; 78: 130-140. https://doi.org/10.1016/j.fct.2015.02.011
  23. Hirt N, Body-Malapel M. Immunotoxicity and intestinal effects of nano- and microplastics: a review of the literature. Part Fibre Toxicol. 2020; 17(1): 57.
  24. Lu K, Qiao R, An H, Zhang Y. Influence of microplastics on the accumulation and chronic toxic effects of cadmium in zebrafish (Danio rerio). Chemosphere. 2018; 202: 514-520. https://doi.org/10.1016/j.chemosphere.2018.03.145
  25. Banaee M, Soltanian S, Sureda A, Gholamhosseini A, Haghi BN, Akhlaghi M, et al. Evaluation of single and combined effects of cadmium and micro-plastic particles on biochemical and immunological parameters of common carp (Cyprinus carpio). Chemosphere. 2019; 236: 124335.
  26. Liu S, Huang J, Zhang W, Shi L, Yi K, Yu H, et al. Microplastics as a vehicle of heavy metals in aquatic environments: a review of adsorption factors, mechanisms, and biological effects. J Environ Manage. 2022; 302(Pt A): 113995.
  27. Park TJ, Lee SH, Lee MS, Lee JK, Lee SH, Zoh KD. Occurrence of microplastics in the Han River and riverine fish in South Korea. Sci Total Environ. 2020; 708: 134535.
  28. Park EJ, Han JS, Park EJ, Seong E, Lee GH, Kim DW, et al. Repeated-oral dose toxicity of polyethylene microplastics and the possible implications on reproduction and development of the next generation. Toxicol Lett. 2020; 324: 75-85. https://doi.org/10.1016/j.toxlet.2020.01.008
  29. Snyder JE, Filipov NM, Parsons PJ, Lawrence DA. The efficiency of maternal transfer of lead and its influence on plasma IgE and splenic cellularity of mice. Toxicol Sci. 2000; 57(1): 87-94. https://doi.org/10.1093/toxsci/57.1.87
  30. Dong C, Flavell RA. Cell fate decision: T-helper 1 and 2 subsets in immune responses. Arthritis Res. 2000; 2(3): 179-188. https://doi.org/10.1186/ar85
  31. Hirano T. IL-6 in inflammation, autoimmunity and cancer. Int Immunol. 2021; 33(3): 127-148. https://doi.org/10.1093/intimm/dxaa078
  32. Rawle DJ, Dumenil T, Tang B, Bishop CR, Yan K, Le TT, et al. Microplastic consumption induces inflammatory signatures in the colon and prolongs a viral arthritis. Sci Total Environ. 2022; 809: 152212.
  33. Kasten-Jolly J, Heo Y, Lawrence DA. Impact of developmental lead exposure on splenic factors. Toxicol Appl Pharmacol. 2010; 247: 105-115. https://doi.org/10.1016/j.taap.2010.06.003
  34. Miller TE, Golemboski KA, Ha RS, Bunn T, Sanders FS, Dietert RR. Developmental exposure to lead causes persistent immunotoxicity in Fischer 344 rats. Toxicol Sci. 1998; 42(2): 129-135. https://doi.org/10.1093/toxsci/42.2.129
  35. Jiang X, Guan S, Qiao Y, Li X, Xu Y, Yang L, et al. Effects of poly(I:C) and MF59 co-adjuvants on immunogenicity and efficacy of survivin polypeptide immunogen against melanoma. J Cell Physiol. 2018; 233(6): 4926-4934. https://doi.org/10.1002/jcp.26317
  36. Zhao X, Liu J, Ge S, Chen C, Li S, Wu X, et al. Saikosaponin A inhibits breast cancer by regulating Th1/Th2 balance. Front Pharmacol. 2019; 10: 624.
  37. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005; 201(2): 233-240. https://doi.org/10.1084/jem.20041257
  38. Liu J, McCauley L, Yan C, Shen X, Pinto-Martin JA. Low blood lead levels and hemoglobin concentrations in preschool children in China. Toxicol Environ Chem. 2012; 94(2): 423-426. https://doi.org/10.1080/02772248.2011.628001
  39. Lee YB, Kim GW, Song YM, Han YH, Ha CS, Lee JS, et al. Preventive effect of garlic administration on respiratory toxicity induced through intratracheal instillation of fine dust (PM10) in rats. J Environ Health Sci. 2020; 46(6): 667-675.