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Evaluating the Apoptotic Cell Death Modulatory Activity of Nanoparticles in Men and Women Neutrophils and Eosinophils

Inflammation volume 45, pages 387–398 (2022)Cite this article

Abstract—

Apoptosis is an important cell death mechanism for the resolution of inflammation. Neutrophil spontaneous apoptosis rates were reported to be slightly different in men and women and to be modulated by female sex hormones. The aim of this study was to determine whether different nanoparticles (NPs) will alter the neutrophil and eosinophil apoptotic rates differently in men and women. Using the antiapoptotic cytokine granulocyte–macrophage colony-stimulating factor (GM-CSF) and the proapoptotic plant lectin Viscum album agglutinin-I (VAA-I) as controls, we found that these factors respectively delay and induce apoptosis in both neutrophils and eosinophils with apoptotic rates remarkably similar in both sexes. The polyamidoamine (PAMAM) dendrimers of generation 0 (G0) and G3 slightly, but not significantly, accelerate neutrophil apoptosis regardless of sex. Zinc oxide (ZnO), titanium dioxide (TiO2), cerium dioxide (CeO2), and palladium (Pd) but not platinum (Pt) NPs were found to significantly delay neutrophil apoptosis. When results were compared between men and women, only ZnO and Pd NPs were found to significantly delay neutrophil apoptosis in men while ZnO, TiO2, CeO2, and Pt NPs inhibit apoptosis in women neutrophils. In eosinophils, G3, but not G0 NPs, significantly accelerate apoptosis in women. ZnO, Pt, and Pd NPs significantly delay eosinophil apoptosis but only in women. Unlike neutrophils, TiO2 and CeO2 NPs did not significantly delay eosinophil apoptosis. We propose that future studies aiming at determining potential effect NPs on cellular biological processes should incorporate a sex-based analysis based on the differences reported here studying the impact of NPs on human granulocyte apoptosis.

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References

  1. Jaillon, S., K. Berthenet, and C. Garlanda. 2019. Sexual dimorphism in innate immunity. Clinical reviews in allergy & immunology 56: 308–321.

    Article  CAS  Google Scholar 

  2. Lefevre, N., F. Corazza, J. Valsamis, A. Delbaere, V. De Maertelaer, J. Duchateau, and G. Casimir. 2019. The number of X chromosomes influences inflammatory cytokine production following toll-like receptor stimulation. Frontiers in immunology 10: 1052.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Liew, P.X., and P. Kubes. 2019. The neutrophil’s role during health and disease. Physiological reviews 99: 1223–1248.

    Article  CAS  PubMed  Google Scholar 

  4. Ratajczak-Wrona, W., K. Nowak, M. Garley, K. Grubczak, D. Dabrowska, A. Iwaniuk, S. Wilk, M. Moniuszko, J. Czerniecki, S. Wolczynski, and E. Jablonska. 2019. Expression of serine proteases in neutrophils from women and men: regulation by endocrine disruptor bisphenol A. Environmental toxicology and pharmacology 71: 103212.

  5. Ratajczak-Wrona, W., M. Garley, M. Rusak, K. Nowak, J. Czerniecki, K. Wolosewicz, M. Dabrowska, S. Wolczynski, P. Radziwon, and E. Jablonska. 2021. Sex-dependent dysregulation of human neutrophil responses by bisphenol A. Environmental health 20: 5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pace, S., A. Rossi, V. Krauth, F. Dehm, F. Troisi, R. Bilancia, C. Weinigel, S. Rummler, O. Werz, and L. Sautebin. 2017. Sex differences in prostaglandin biosynthesis in neutrophils during acute inflammation. Scientific reports 7: 3759.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Brach, M.A., S. deVos, H.J. Gruss, and F. Herrmann. 1992. Prolongation of survival of human polymorphonuclear neutrophils by granulocyte-macrophage colony-stimulating factor is caused by inhibition of programmed cell death. Blood 80: 2920–2924.

    Article  CAS  PubMed  Google Scholar 

  8. Lavastre, V., M. Pelletier, R. Saller, K. Hostanska, and D. Girard. 2002. Mechanisms involved in spontaneous and Viscum album agglutinin-I-induced human neutrophil apoptosis: Viscum album agglutinin-I accelerates the loss of antiapoptotic Mcl-1 expression and the degradation of cytoskeletal paxillin and vimentin proteins via caspases. Journal of immunology 168: 1419–1427.

    Article  CAS  Google Scholar 

  9. Babin, K., F. Antoine, D.M. Goncalves, and D. Girard. 2013. TiO2, CeO2 and ZnO nanoparticles and modulation of the degranulation process in human neutrophils. Toxicology letters 221: 57–63.

    Article  CAS  PubMed  Google Scholar 

  10. Chhay, P., M. Murphy-Marion, Y. Samson, and D. Girard. 2018. Activation of human eosinophils with palladium nanoparticles (Pd NPs): Importance of the actin cytoskeleton in Pd NPs-induced cellular adhesion. Environmental toxicology and pharmacology 57: 95–103.

    Article  CAS  PubMed  Google Scholar 

  11. Durocher, I., and D. Girard. 2016. In vivo proinflammatory activity of generations 0–3 (G0–G3) polyamidoamine (PAMAM) nanoparticles. Inflammation research 65: 745–755.

    Article  CAS  PubMed  Google Scholar 

  12. Goncalves, D.M., S. Chiasson, and D. Girard. 2010. Activation of human neutrophils by titanium dioxide (TiO2) nanoparticles. Toxicology in vitro 24: 1002–1008.

    Article  CAS  PubMed  Google Scholar 

  13. Goncalves, D.M., and D. Girard. 2014. Zinc oxide nanoparticles delay human neutrophil apoptosis by a de novo protein synthesis-dependent and reactive oxygen species-independent mechanism. Toxicology in vitro 28: 926–931.

    Article  CAS  PubMed  Google Scholar 

  14. Murphy-Marion, M., and D. Girard. 2018. Titanium dioxide nanoparticles induce human eosinophil adhesion onto endothelial EA.hy926 cells via activation of phosphoinositide 3-kinase/Akt cell signalling pathway. Immunobiology 223: 162–170.

    Article  CAS  PubMed  Google Scholar 

  15. Silva, L.R., and D. Girard. 2016. Human eosinophils are direct targets to nanoparticles: Zinc oxide nanoparticles (ZnO) delay apoptosis and increase the production of the pro-inflammatory cytokines IL-1beta and IL-8. Toxicology letters 259: 11–20.

    Article  CAS  PubMed  Google Scholar 

  16. Lavastre, V., S. Chiasson, H. Cavalli, and D. Girard. 2005. Viscum album agglutinin-I induces apoptosis and degradation of cytoskeletal proteins via caspases in human leukaemia eosinophil AML14.3D10 cells: Differences with purified human eosinophils. British Journal of Haematology 130: 527–535.

    Article  CAS  PubMed  Google Scholar 

  17. Noel, C., J.C. Simard, and D. Girard. 2016. Gold nanoparticles induce apoptosis, endoplasmic reticulum stress events and cleavage of cytoskeletal proteins in human neutrophils. Toxicology in vitro 31: 12–22.

    Article  CAS  PubMed  Google Scholar 

  18. Simard, J.C., M.M. Simon, P.A. Tessier, and D. Girard. 2011. Damage-associated molecular pattern S100A9 increases bactericidal activity of human neutrophils by enhancing phagocytosis. Journal of immunology 186: 3622–3631.

    Article  CAS  Google Scholar 

  19. Bohmer, N., A. Rippl, S. May, A. Walter, M.B. Heo, M. Kwak, M. Roesslein, N.W. Song, P. Wick, and C. Hirsch. 2018. Interference of engineered nanomaterials in flow cytometry: A case study. Colloids and surfaces. B, Biointerfaces 172: 635–645.

    Article  CAS  PubMed  Google Scholar 

  20. Molloy, E.J., A.J. O’Neill, J.J. Grantham, M. Sheridan-Pereira, J.M. Fitzpatrick, D.W. Webb, and R.W. Watson. 2003. Sex-specific alterations in neutrophil apoptosis: The role of estradiol and progesterone. Blood 102: 2653–2659.

    Article  CAS  PubMed  Google Scholar 

  21. Fresneda Alarcon, M., Z. McLaren, and H. L. Wright. 2021. Neutrophils in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus: same foe different M.O. Frontiers in immunology 12: 649693.

  22. Pérez-Figueroa, E., P. Álvarez-Carrasco, E. Ortega, and C. Maldonado-Bernal. 2021. Neutrophils: many ways to die. Frontiers in immunology 12: 631821.

  23. Shi, J., and J. Li. 2020. Neutrophil-targeted engineered prodrug nanoparticles for anti-inflammation. FASEB journal 34: 9828–9831.

    Article  CAS  PubMed  Google Scholar 

  24. Xia, Q., J. Huang, Q. Feng, X. Chen, X. Liu, X. Li, T. Zhang, S. Xiao, H. Li, Z. Zhong, and K. Xiao. 2019. Size- and cell type-dependent cellular uptake, cytotoxicity and in vivo distribution of gold nanoparticles. International journal of nanomedicine 14: 6957–6970.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhang, C.Y., X. Dong, J. Gao, W. Lin, Z. Liu, and Z. Wang. 2019. Nanoparticle-induced neutrophil apoptosis increases survival in sepsis and alleviates neurological damage in stroke. Science advances 5: eaax7964.

  26. Durocher, I., C. Noel, V. Lavastre, and D. Girard. 2017. Evaluation of the in vitro and in vivo proinflammatory activities of gold (+) and gold (-) nanoparticles. Inflammation research 66: 981–992.

    Article  CAS  PubMed  Google Scholar 

  27. Kwemo, P.S.A., M. Vanharen, I. Durocher, D. Girard. 2020. Impact of palladium nanoparticles (Pd-NPs) on the biology of neutrophils in vitro and on leukocyte attraction in vivo. Journal of Nanoparticle Research 22.

  28. Liz, R., J.C. Simard, L.B. Leonardi, and D. Girard. 2015. Silver nanoparticles rapidly induce atypical human neutrophil cell death by a process involving inflammatory caspases and reactive oxygen species and induce neutrophil extracellular traps release upon cell adhesion. International immunopharmacology 28: 616–625.

    Article  CAS  PubMed  Google Scholar 

  29. Poirier, M., J.C. Simard, F. Antoine, and D. Girard. 2014. Interaction between silver nanoparticles of 20 nm (AgNP20) and human neutrophils: Induction of apoptosis and inhibition of de novo protein synthesis by AgNP20 aggregates. Journal of applied toxicology 34: 404–412.

    Article  CAS  PubMed  Google Scholar 

  30. Poirier, M., J. C. Simard, and D. Girard. 2015. Silver nanoparticles of 70 nm and 20 nm affect differently the biology of human neutrophils. J Immunotoxicol 1–11.

  31. Thomas, C.J., and K. Schroder. 2013. Pattern recognition receptor function in neutrophils. Trends in immunology 34: 317–328.

    Article  CAS  PubMed  Google Scholar 

  32. Kvarnhammar, A.M., and L.O. Cardell. 2012. Pattern-recognition receptors in human eosinophils. Immunology 136: 11–20.

    CAS  PubMed  Google Scholar 

  33. Pallardy, M.J., I. Turbica, and A. Biola-Vidamment. 2017. Why the immune system should be concerned by nanomaterials? Frontiers in immunology 8: 544.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Behzadi, S., V. Serpooshan, W. Tao, M.A. Hamaly, M.Y. Alkawareek, E.C. Dreaden, D. Brown, A.M. Alkilany, O.C. Farokhzad, and M. Mahmoudi. 2017. Cellular uptake of nanoparticles: Journey inside the cell. Chemical Society reviews 46: 4218–4244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Arruda, M.A., and C. Barja-Fidalgo. 2009. NADPH oxidase activity: In the crossroad of neutrophil life and death. Frontiers in bioscience 14: 4546–4556.

    Article  CAS  Google Scholar 

  36. Pujari-Palmer, S., S. Chen, S. Rubino, H. Weng, W. Xia, H. Engqvist, L. Tang, and M.K. Ott. 2016. In vivo and in vitro evaluation of hydroxyapatite nanoparticle morphology on the acute inflammatory response. Biomaterials 90: 1–11.

    Article  CAS  PubMed  Google Scholar 

  37. Couto, D., M. Freitas, V. Vilas-Boas, I. Dias, G. Porto, M.A. Lopez-Quintela, J. Rivas, P. Freitas, F. Carvalho, and E. Fernandes. 2014. Interaction of polyacrylic acid coated and non-coated iron oxide nanoparticles with human neutrophils. Toxicology letters 225: 57–65.

    Article  CAS  PubMed  Google Scholar 

  38. Simon, H.U. 2001. Regulation of eosinophil and neutrophil apoptosis–similarities and differences. Immunological reviews 179: 156–162.

    Article  CAS  PubMed  Google Scholar 

  39. Daigle, I., and H.U. Simon. 2001. Critical role for caspases 3 and 8 in neutrophil but not eosinophil apoptosis. International archives of allergy and immunology 126: 147–156.

    Article  CAS  PubMed  Google Scholar 

  40. Liles, W.C., D.C. Dale, and S.J. Klebanoff. 1995. Glucocorticoids inhibit apoptosis of human neutrophils. Blood 86: 3181–3188.

    Article  CAS  PubMed  Google Scholar 

  41. McColl, A., S. Michlewska, I. Dransfield, and A.G. Rossi. 2007. Effects of glucocorticoids on apoptosis and clearance of apoptotic cells. TheScientificWorldJOURNAL 7: 1165–1181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Meagher, L.C., J.M. Cousin, J.R. Seckl, and C. Haslett. 1996. Opposing effects of glucocorticoids on the rate of apoptosis in neutrophilic and eosinophilic granulocytes. Journal of immunology 156: 4422–4428.

    Article  CAS  Google Scholar 

  43. Taylor, E.L., I.L. Megson, C. Haslett, and A.G. Rossi. 2003. Nitric oxide: A key regulator of myeloid inflammatory cell apoptosis. Cell death and differentiation 10: 418–430.

    Article  CAS  PubMed  Google Scholar 

  44. Vanharen, M., and D. Girard. 2020. Activation of human eosinophils with nanoparticles: A new area of research. Inflammation 43: 8–16.

    Article  PubMed  Google Scholar 

  45. Janaszewska, A., M. Ciolkowski, D. Wróbel, J.F. Petersen, M. Ficker, J.B. Christensen, M. Bryszewska, and B. Klajnert. 2013. Modified PAMAM dendrimer with 4-carbomethoxypyrrolidone surface groups reveals negligible toxicity against three rodent cell-lines. Nanomedicine : Nanotechnology, biology, and medicine 9: 461–464.

    Article  CAS  Google Scholar 

  46. Mukherjee, S.P., F.M. Lyng, A. Garcia, M. Davoren, and H.J. Byrne. 2010. Mechanistic studies of in vitro cytotoxicity of poly(amidoamine) dendrimers in mammalian cells. Toxicology and applied pharmacology 248: 259–268.

    Article  CAS  PubMed  Google Scholar 

  47. Naha, P.C., M. Davoren, F.M. Lyng, and H.J. Byrne. 2010. Reactive oxygen species (ROS) induced cytokine production and cytotoxicity of PAMAM dendrimers in J774A.1 cells. Toxicology and applied pharmacology 246: 91–99.

    Article  CAS  PubMed  Google Scholar 

  48. Miyagi, M., H. Aoyama, M. Morishita, and Y. Iwamoto. 1992. Effects of sex hormones on chemotaxis of human peripheral polymorphonuclear leukocytes and monocytes. Journal of periodontology 63: 28–32.

    Article  CAS  PubMed  Google Scholar 

  49. Bouman, A., M.J. Heineman, and M.M. Faas. 2005. Sex hormones and the immune response in humans. Human reproduction update 11: 411–423.

    Article  CAS  PubMed  Google Scholar 

  50. Ray, J. L., P. Fletcher, R. Burmeister, and A. Holian. 2020. The role of sex in particle-induced inflammation and injury. Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology 12: e1589.

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Funding

The study was supported by grants (2017–0044) from the Institut de recherche Robert-Sauvé en santé et en sécurité du travail (IRSST).

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Authors and Affiliations

  1. Laboratoire de Recherche en Inflammation Et Physiologie Des Granulocytes, Université du Québec, INRS-Centre Armand-Frappier Santé Biotechnologie, 531 Boul. des Prairies, Laval, QC, H7V 1B7, Canada

    Marion Vanharen, Isabelle Durocher, Abdelaziz Saafane & Denis Girard

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  1. Marion Vanharen
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  2. Isabelle Durocher
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  3. Abdelaziz Saafane
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  4. Denis Girard
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MV, ID, and AS carried out the experiments and plotted and analyzed the data. DG wrote the manuscript with support from MV, ID, and AS and is the supervisor of the project.

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Correspondence to Denis Girard.

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Vanharen, M., Durocher, I., Saafane, A. et al. Evaluating the Apoptotic Cell Death Modulatory Activity of Nanoparticles in Men and Women Neutrophils and Eosinophils. Inflammation 45, 387–398 (2022). https://doi.org/10.1007/s10753-021-01553-5

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