Cell Biology and Toxicology

, Volume 19, Issue 3, pp 145–159

Comparative particle-induced cytotoxicity toward macrophages and fibroblasts

  • V. Olivier
  • J.-L. Duval
  • M. Hindié
  • P. Pouletaut
  • M.-D. Nagel
Article

Abstract

The cytotoxicity caused by the debris resulting from wear of prostheses can produce major damage to tissues around the implant. We have compared particle internalization by macrophages and fibroblastsin vitro and analyzed cell death. J774.2 macrophages and L929 fibroblasts were incubated with 0.43 and 2.81 μm alumina particles or 0.45 and 3.53 μm polystyrene (PS) beads. Incubation of J774.2 cells with alumina particles of both sizes and 0.5 and 1.0 mg/ml PS beads significantly decreased cell numbers in a particle concentration-dependent manner. L929 cells were not affected by lower concentrations of 0.43 μm alumina particles (which aggregate at high concentrations) and they internalized 0.45 μm PS beads without any decrease in cell numbers. Particles were more cytotoxic for macrophages than for fibroblasts. Particles caused the size of both types of cells to increase in correlation with cytotoxicity. Trypan blue exclusion and lactate dehydrogenase release showed cell membrane leakage for both types of cells incubated with PS beads for 24 h. Apoptosis was assessed by annexin V–FITC, propidium iodide staining and assay of caspase 3 activity. Macrophage death appeared to depend on both necrosis, caused mainly by 3.53 μm PS beads, and apoptosis, mainly due to 0.45 μm PS beads. The release of the inflammatory cytokine IL-6 appears to be nonlinearly correlated with cytotoxicity. Thus, the size of the internalized particles affects macrophages and fibroblasts differently, and the increase in cell size can be used as a preliminary criterion of particle cytotoxicityin vitro.

apoptosis cell size cell viability IL6 necrosis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bentley SA, Tralka TS, Alabaster O. Phagocytic properties of bone marrow fibroblasts. Exp Hematol. 1981;9:313-18.Google Scholar
  2. Catelas I, Huk OL, Petit A, Zukor DJ, Marchand R, Yahia L. Flow cytometric analysis of macrophage response to ceramic and polyethylene particles: effects of size, concentration, and composition. J Biomed Mater Res. 1998;41:600-7.Google Scholar
  3. Catelas I, Petit A, Zukor DJ, Marchand R, Yahia L, Huk OL. Induction of macrophage apoptosis by ceramic and polyethylene particles in vitro. Biomaterials. 1999a;20:625-30.Google Scholar
  4. Catelas I, Petit A, Marchand R, Zukor DJ, Yahia L, Huk OL. Cytotoxicity and macrophage cytokine release induced by ceramic and polyethylene particles in vitro. J Bone Joint Surg Br. 1999b;81:516-21.Google Scholar
  5. Catelas I, Petit A, Zukor DJ, Antoniou J, Huk OL. TNF-alpha secretion and macrophage mortality induced by cobalt and chromium ions in vitro -- qualitative analysis of apoptosis. Biomaterials. 2003;24:383-91.Google Scholar
  6. Ciapetti G, Savarino L, Giunti A, et al. Effects of two-FE-based superalloy particles on osteoblast-and macrophages-like cells. 17th European Society for Biomaterials Conference, Barcelona, Spain. 2002.Google Scholar
  7. Decker T, Lohmann-Matthes ML. A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods. 1988;115:61-9.Google Scholar
  8. Evans EJ. Cell damage in vitro following direct contact with fine particles of titanium, titanium alloy and cobalt-chrome-molybdenum alloy. Biomaterials. 1994;15:713-17.Google Scholar
  9. Frondoza CG, Tanner KT, Jones LC, Hungerford DS. Polymethylmethacrylate particles enhance DNA and protein synthesis of human fibroblasts in vitro. J Biomed Mater Res. 1993;27:611-17.Google Scholar
  10. Germain MA, Hatton A, Williams S, et al. Comparison of the cytotoxicity of clinically relevant cobalt-chromium and alumina ceramic wear particles in vitro. Biomaterials. 2003;24:469-79.Google Scholar
  11. Glant TT, Jacobs JJ, Mikecz K, et al. Particulate-induced, prostaglandin-and cytokine-mediated bone resorption in an experimental system and in failed joint replacements. Am J Ther. 1996;3:27-41.Google Scholar
  12. Green TR, Fisher J, Stone M, Wroblewski BM, Ingham E. Polyethylene particles of a “critical size” are necessary for the induction of cytokines by macrophages in vitro. Biomaterials. 1998;19:2297-302.Google Scholar
  13. Greis PE, Georgescu HI, Fu FH, Evans CH. Particle-induced synthesis of collagenase by synovial fibroblasts: an immunocytochemical study. J Orthop Res. 1994;12:286-93.Google Scholar
  14. Hatton A, Nevelos JE, Nevelos AA, Banks RE, Fisher J, Ingham E. Alumina-alumina artificial hip joints. Part I: a histological analysis and characterisation of wear debris by laser capture microdissection of tissues retrieved at revision. Biomaterials. 2002;23:3429-40.Google Scholar
  15. Henssge EJ, Bos I, Willman G. A12O3 angainst A12O3 combination in hip endoprostheses. Histologic investigations with semi-quantitative grading of revision and autopsy cases and abrasion measures. J Mater Sci Mater Med. 1994;5:657-61.Google Scholar
  16. Homburg CH, de Haas M, von dem Borne AE, Verhoeven AJ, Reutelingsperger CP, Roos D. Human neutrophils lose their surface Fc gamma RIII and acquire Annexin V binding sites during apoptosis in vitro. Blood. 1995; 85: 532-40.Google Scholar
  17. Horowitz SM, Luchetti WT, Gonzales JB, Ritchie CK. The effect of cobalt chromium upon macrophages. J Biomed Mater Res. 1998;41:468-73.Google Scholar
  18. Humphreys DT, Wilson MR. Modes of L929 cell death induced by TNF-alpha and other cytotoxic agents. Cytokine. 1999;11:773-82.Google Scholar
  19. Huppertz B, Frank HG, Kaufmann P. The apoptosis cascade morphological and immunohistochemical methods for its visualization. Anat Embryol. 1999;200:1-18.Google Scholar
  20. Kadoya Y, Kobayashi A, Ohashi H. Wear and osteolysis in total joint replacements. Acta Orthop Scand Suppl. 1998;278:1-16.Google Scholar
  21. Karpinish NO, Tafani M, Rothman RJ, Russo MA, Farber JL. The course of etoposide-induced apoptosis from damage to DNA and p53 activation to mitochondrial release of cytochrome c. J Biol Chem. 2002;277:16547-52.Google Scholar
  22. Kohilas K, Lyons M, Lofthouse R, Frondoza CG, Jinnah R, Hungerford DS. Effect of prosthetic titanium wear debris on mitogen-induced monocyte and lymphoid activation. J Biomed Mater Res. 1999;47:95-103.Google Scholar
  23. Korzeniewski C, Callewaert DM. An enzyme-release assay for natural cytotoxicity. J Immunol Methods. 1983;64: 313-20.Google Scholar
  24. Lind M, Trindade MC, Yaszay B, Goodman SB, Smith RL. Effects of particulate debris on macrophage-dependent fibroblast stimulation in coculture. J Bone Joint Surg. 1998;80:924-30.Google Scholar
  25. Los M, Mozoluk M, Ferrari D, et al. Activation and caspase-mediated inhibition of PARP: a molecular switch between fibroblast necrosis and apoptosis in death receptor signaling. Mol Biol Cell. 2002;13: 978-88.Google Scholar
  26. Matthews JB, Besong AA, Green TR, et al. Evaluation of the response of primary human peripheral blood mononuclear phagocytes to challenge with in vitro generated clinically relevant UHMWPE particles of known size and dose. J Biomed Mater Res. 2000;52:296-307.Google Scholar
  27. Manlapaz M, Maloney WJ, Smith RL. In vitro activation of human fibroblasts by retrieved titanium alloy wear debris. J Orthop Res. 1996;14:465-4-2.Google Scholar
  28. McConkey DJ. Biochemical determinants of apoptosis and necrosis. Toxicol Lett. 1998;99:157-68.Google Scholar
  29. Morhenn VB, Lemperle G, Gallo RL. Phagocytosis of different particulate dermal filler substances by human macrophages and skin cells. Dermatol Surg. 2002;28:484-90.Google Scholar
  30. Mostardi RA, Meerbaum SO, Kovacik MW, Gradisar IA Jr. Response of human fibroblasts to tantalum and titanium in cell culture. Biomed Sci Instrum. 1997;33:514-18.Google Scholar
  31. Mostardi RA, Meerbaum SO, Kovacik MW, Gradisar IA Jr. In vitro response of human fibroblasts to commercially pure titanium. J Biomed Mater Res. 1999;47:60-4.Google Scholar
  32. Ninomiya JT, Struve JA, Stelloh CT, Toth JM, Crosby KE. Effect of hydroxyapatite particulate debris on the production of cytokines and proteases in human fibroblasts. J Orthop Res. 2001;19:621-8.Google Scholar
  33. Osano E, Kishi J, Takahashi Y. Phagocytosis of titanium particles and necrosis in TNF-alpha-resistant mouse sarcoma L929 cells. Toxicol In Vitro. 2003;17:41-7.Google Scholar
  34. Petit A, Catelas I, Antoniou J, Zukor DJ, Huk OL. Differential apoptotic response of J774 macrophages to alumina and ultra-high-molecular-weight polyethylene particles. J Orthop Res. 2002;20: 9-15.Google Scholar
  35. Prabhu A, Shelburne CE, Gibbons DF. Cellular proliferation and cytokine responses of murine macrophage cell line J774 A.1 to polymethylmethacrylate and cobalt-chrome alloy particles. J Biomed Mater Res. 1998;42:655-63.Google Scholar
  36. Renwick LC, Donaldson K, Clouter A. Impairment of alveolar macrophage phagocytosis by ultrathin particles. Toxicol Appl Pharmacol. 2001;172:119-27.Google Scholar
  37. Ruetten H, Thiemermann C. Interleukin-13 is a more potent inhibitor of the expression of inducible nitric oxide synthase in smooth muscle cells than in macrophages: a comparison with interleukin-4 and interleukin-10. Shock 1997;8:409-14.Google Scholar
  38. Salzman GC, Singham SB, Johnston RG, Bohren CF. Light scattering and cytometry. In: Melamed MR, Lindmo T, Mendelsohn ML, eds. Flow cytometry and sorting. New York: Wiley-Liss; 1990:81-107.Google Scholar
  39. Shanbhag AS, Jacobs JJ, Black J, Galante JO, Glant TT. Macrophage/particle interactions: effect of size, composition and surface area. J Biomed Mater Res. 1994;28:81-90.Google Scholar
  40. Shim SR, Kook S, Kim JI, Song WK. Degradation of focal adhesion proteins paxillin and p 130cas by caspases or calpains in apoptotic rat-1 and L929 cells. Biochem Biophys Res Commun. 2001;24:601-8.Google Scholar
  41. Stea S, Visentin M, Granchi D, et al. Apoptosis in peri-implant tissue. Biomaterials. 2000;21:1393-8.Google Scholar
  42. Stoika R, Kashchak N, Lutsik-Kordovsky M, Boyko M, Tsyrulnyk A. In vitro response of phagocytic cells to immunomodulating agents. Med Sci Monit. 2001;7:652-8.Google Scholar
  43. Tengku-Muhammad TS, Cryer A, Ramji DP. Synergism between interferon gamma and tumor necrosis factor alpha in the regulation of lipoprotein lipase in the macrophage J774.2 cell line. Cytokine. 1998;10:38-48.Google Scholar
  44. Tengku-Muhammad TS, Hughes TR, Cryer A, Ramji DP. Involvement of both the tyrosine kinase and the phosphatidylinositol-3′ kinase signal transduction pathways in the regulation of lipoprotein lipase expresion in J774.2 macrophages by cytokines and lipopolysaccharide. Cytokine. 1999;11:463-8.Google Scholar
  45. Torché AM, Albina E, Le Corre P, Jestin A, Le Verge R. Flow cytometric and optical microscopic evaluation of poly(D,L-lactide-co-glycolide) microspheres phagocytosis by pig alveolar macrophages. J Control Release. 1999;58:289-301.Google Scholar
  46. Trindade MC, Schurman DJ, Maloney WJ, Goodman SB, Smith RL. G-protein activity requirement for polymethylmethacrylate and titanium particule-induced fibroblast interleukin-6 and monocyte chemoattractant protein-1 release in vitro. J Biomed Mater Res. 2000;51:360-8.Google Scholar
  47. Trindade MC, Lind M, Sun D, Schurman DJ, Goodman SB, Smith RL. In vitro reaction to orthopaedic biomaterials by macrophages and lymphocytes isolated from patients under-going revision surgery. Biomaterials 2001a;22:253-9.Google Scholar
  48. Trindade MC, Lind M, Nakashima Y, et al. Interleukin-10 inhibits polymethylmethacrylate particle induced interleukin-6 and tumor necrosis factor-alpha release by human monocyte/macrophages in vitro. Biomaterials. 2001b;22:2067-73.Google Scholar
  49. Vercammen D, Brouckaert G, Denecker G, et al. Dual signaling of the Fas receptor: initiation of both apoptotic and necrotic cell death pathways. J Exp Med. 1998;188:919-30.Google Scholar
  50. Verhoven B, Schlegel RA, Williamson P. Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lymphocytes. J Exp Med. 1995;182:1597-601.Google Scholar
  51. Vermes I, Haanen C, Steffens-Nakken H, Reutelingsperger C. A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods. 1995;184:39-51.Google Scholar
  52. Yao J, Glant TT, Lark MW, et al. The potential role of fibroblasts in periprosthetic osteolysis: fibroblast response to titanium particles. J Bone Miner Res. 1995;10:1417-27.Google Scholar
  53. Yoon TR, Rowe SM, Jung ST, Seon KJ, Maloney WJ. Osteolysis in association with a total hip arthroplasty with ceramic bearing surfaces. J Bone Joint Surg Am. 1998;80:1459-68.Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • V. Olivier
    • 1
  • J.-L. Duval
    • 1
  • M. Hindié
    • 1
  • P. Pouletaut
    • 1
  • M.-D. Nagel
    • 1
  1. 1.UMR CNRS 6600University of Technology of CompiègneCompiègneFrance

Personalised recommendations