Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Article
  • Published:

Macrophage polarization in response to wear particles in vitro

Cellular & Molecular Immunology volume 10, pages 471–482 (2013)Cite this article

Abstract

Total joint replacement is a highly successful surgical procedure for treatment of patients with disabling arthritis and joint dysfunction. However, over time, with high levels of activity and usage of the joint, implant wear particles are generated from the articulating surfaces. These wear particles can lead to activation of an inflammatory reaction, and subsequent bone resorption around the implant (periprosthetic osteolysis). Cells of the monocyte/macrophage lineage orchestrate this chronic inflammatory response, which is dominated by a pro-inflammatory (M1) macrophage phenotype rather than an anti-inflammatory pro-tissue healing (M2) macrophage phenotype. While it has been shown that interleukin-4 (IL-4) selectively polarizes macrophages towards an M2 anti-inflammatory phenotype which promotes bone healing, rather than inflammation, little is known about the time course in which this occurs or conditions in which repolarization through IL-4 is most effective. The goal of this work was to study the time course of murine macrophage polarization and cytokine release in response to challenge with combinations of polymethyl methacrylate (PMMA) particles, lipopolysaccharide (LPS) and IL-4 in vitro. Treatment of particle-challenged monocyte/macrophages with IL-4 led to an initial suppression of pro-inflammatory cytokines and inducible nitric oxide synthase (iNOS) production and subsequent polarization into an M2 anti-inflammatory phenotype. This result was optimized when IL-4 was delivered before PMMA particle challenge, to an M1 phenotype rather than to uncommitted (M0) macrophages. The effects of this polarization were sustained over a 5-day time course. Polarization of M1 macrophages into an M2 phenotype may be a strategy to mitigate wear particle associated periprosthetic osteolysis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Harris WH . Wear and periprosthetic osteolysis: the problem. Clin Orthop Relat Res 2001; 393: 66–70.

    Article  Google Scholar 

  2. Amstutz HC, Campbell P, Kossovsky N, Clarke IC . Mechanism and clinical significance of wear debris-induced osteolysis. Clin Orthop Relat Res 1992; 276: 7–18.

    Google Scholar 

  3. Schmalzried TP, Jasty M, Harris WH . Periprosthetic bone loss in total hip arthroplasty. Polyethylene wear debris and the concept of the effective joint space. J Bone Joint Surg Am 1992; 74: 849–863.

    Article  CAS  PubMed  Google Scholar 

  4. Hirakawa K, Bauer TW, Stulberg BN, Wilde AH . Comparison and quantitation of wear debris of failed total hip and total knee arthroplasty. J Biomed Mater Res 1996; 31: 257–263.

    Article  CAS  PubMed  Google Scholar 

  5. Margevicius KJ, Bauer TW, McMahon JT, Brown SA, Merritt K . Isolation and characterization of debris in membranes around total joint prostheses. J Bone Joint Surg Am 1994; 76: 1664–1675.

    Article  CAS  PubMed  Google Scholar 

  6. Schwarz EM, Benz EB, Lu AP, Goater JJ, Mollano AV, Rosier RN et al. Quantitative small animal surrogate to evaluate drug efficacy in preventing wear debris-induced osteolysis. J Orthop Res 2000; 18: 849–855.

    Article  CAS  PubMed  Google Scholar 

  7. Merkel KD, Erdmann JM, McHugh KP, Abu-Amer Y, Ross FP, Teitelbaum SL . Tumor necrosis factor-alpha mediates orthopedic implant osteolysis. Am J Pathol 1999; 154: 203–210.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Shanbhag AS, Hasselman CT, Rubash HE . The John Charnley Award. Inhibition of wear debris mediated osteolysis in a canine total hip arthroplasty model. Clin Orthop Relat Res 1997; 344: 33–43.

    Article  Google Scholar 

  9. Wooley PH, Morren R, Andary J, Sud S, Yang SY, Mayton L et al. Inflammatory responses to orthopaedic biomaterials in the murine air pouch. Biomaterials 2002; 23: 517–526.

    Article  CAS  PubMed  Google Scholar 

  10. Blaine TA, Rosier RN, Puzas JE, Looney RJ, Reynolds PR, Reynolds SD et al. Increased levels of tumor necrosis factor-alpha and interleukin-6 protein and messenger RNA in human peripheral blood monocytes due to titanium particles. J Bone Joint Surg Am 1996; 78: 1181–1192.

    Article  CAS  PubMed  Google Scholar 

  11. Nakashima Y, Sun DH, Trindade MC, Maloney WJ, Goodman SB, Schurman DJ et al. Signaling pathways for tumor necrosis factor-alpha and interleukin-6 expression in human macrophages exposed to titanium-alloy particulate debris in vitro. J Bone Joint Surg Am 1999; 81: 603–615.

    Article  CAS  PubMed  Google Scholar 

  12. Ingham E, Green TR, Stone MH, Kowalski R, Watkins N, Fisher J . Production of TNF-alpha and bone resorbing activity by macrophages in response to different types of bone cement particles. Biomaterials 2000; 21: 1005–1013.

    Article  CAS  PubMed  Google Scholar 

  13. Maloney WJ, James RE, Smith RL . Human macrophage response to retrieved titanium alloy particles in vitro. Clin Orthop Relat Res 1996; 322: 268–278.

    Article  Google Scholar 

  14. Goodman SB, Lind M, Song Y, Smith RL . In vitro, in vivo, and tissue retrieval studies on particulate debris. Clin Orthop Relat Res 1998; 352: 25–34.

    Article  Google Scholar 

  15. Goodman SB, Huie P, Song Y, Schurman D, Maloney W, Woolson S et al. Cellular profile and cytokine production at prosthetic interfaces. Study of tissues retrieved from revised hip and knee replacements. J Bone Joint Surg Br 1998; 80: 531–539.

    Article  CAS  PubMed  Google Scholar 

  16. Chiu R, Ma T, Smith RL, Goodman SB . Ultrahigh molecular weight polyethylene wear debris inhibits osteoprogenitor proliferation and differentiation in vitro. J Biomed Mater Res A 2009; 89: 242–247.

    PubMed  Google Scholar 

  17. Gallo J, Goodman SB, Konttinen YT, Raska M . Particle disease: biologic mechanisms of periprosthetic osteolysis in total hip arthroplasty. Innate Immunity 2012; 19: 213–224.

    Article  CAS  PubMed  Google Scholar 

  18. Ren PG, Irani A, Huang Z, Ma T, Biswal S, Goodman SB . Continuous infusion of UHMWPE particles induces increased bone macrophages and osteolysis. Clin Orthop Relat Res 2011; 469: 113–122.

    Article  PubMed  Google Scholar 

  19. Huang Z, Ma T, Ren PG, Smith RL, Goodman SB . Effects of orthopaedic polymer particles on chemotaxis of macrophages and mesenchymal stem cells. J Biomed Mater Res A 2010; 94: 1264–1269.

    PubMed  PubMed Central  Google Scholar 

  20. Ren PG, Huang Z, Ma T, Biswal S, Smith RL, Goodman SB . Surveillance of systemic trafficking of macrophages induced by UHMWPE particles in nude mice by noninvasive imaging. J Biomed Mater Res A 2010; 94: 706–711.

    PubMed  PubMed Central  Google Scholar 

  21. Ren PG, Lee SW, Biswal S, Goodman SB . Systemic trafficking of macrophages induced by bone cement particles in nude mice. Biomaterials 2008; 29: 4760–4765.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Rao AJ, Gibon E, Ma T, Yao Z, Smith RL, Goodman SB . Revision joint replacement wear particles, and macrophage polarization. Acta Biomat 2012; 8: 2815–2823.

    Article  CAS  Google Scholar 

  23. Gordon S . Alternative activation of macrophages. Nat Rev Immunol 2003; 3: 23–35.

    Article  CAS  PubMed  Google Scholar 

  24. Martinez FO, Helming L, Gordon S . Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol 2009; 27: 451–483.

    Article  CAS  PubMed  Google Scholar 

  25. Fairweather D, Cihakova D . Alternatively activated macrophages in infection and autoimmunity. J Autoimmunity 2009; 33: 222–230.

    Article  CAS  Google Scholar 

  26. Ho VW, Sly LM . Derivation and characterization of murine alternatively activated (M2) macrophages. Methods Mol Biol 2009; 531: 173–185.

    Article  CAS  PubMed  Google Scholar 

  27. Murray PJ, Wynn TA . Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol 2011; 11: 723–737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mosser DM, Edwards JP . Exploring the full spectrum of macrophage activation. Nat Rev Immunol 2008; 8: 958–969.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Mantovani A, Sozzani S, Locati M, Allavena P, Sica A . Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 2002; 23: 549–555.

    Article  CAS  PubMed  Google Scholar 

  30. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M . The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 2004; 25: 677–686.

    Article  CAS  PubMed  Google Scholar 

  31. Mantovani A, Garlanda C, Locati M . Macrophage diversity and polarization in atherosclerosis: a question of balance. Arterioscler Thromb Vasc Biol 2009; 29: 1419–1423.

    Article  CAS  PubMed  Google Scholar 

  32. Martinez FO, Gordon S, Locati M, Mantovani A . Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol 2006; 177: 7303–7311.

    Article  CAS  PubMed  Google Scholar 

  33. Martinez FO, Sica A, Mantovani A, Locati M . Macrophage activation and polarization. Front Biosci 2008; 13: 453–461.

    Article  CAS  PubMed  Google Scholar 

  34. Biswas SK, Mantovani A . Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol 2010; 11: 880–896.

    Article  CAS  Google Scholar 

  35. Raes G, de Baestselier P, Noel W, Beschin A, Brombacher F, Hassanzadeh GH . Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages. J Leukoc Biol 2002; 71: 597–602.

    CAS  PubMed  Google Scholar 

  36. Raes G, Noel W, Beschin A, Brys L, de Baetselier P, Hassanzadeh GH . FIZZ1 and Ym as tools to discriminate between differentially activated macrophages. Dev Immunol 2002; 9: 151–159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Maresz K, Ponomarev ED, Barteneva N, Tan Y, Mann MK, Dittel BN . IL-13 induces the expression of the alternative activation marker Ym1 in a subset of testicular macrophages. J Reprod Immunol 2008; 78: 140–148.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Nair MG, Du Y, Perrigoue JG, Zaph C, Taylor JJ, Goldschmidt M et al. Alternatively activated macrophage-derived RELM-a is a negative regulator of type 2 inflammation in the lung. J Exp Med 2009; 206: 937–952.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Brown BN, Ratner BD, Goodman SB, Amar S, Badylak SF . Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine. Biomaterials 2012; 33: 3792–3802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Doyle AG, Herbein G, Montaner LJ, Minty AJ, Caput D, Ferrara P et al. Interleukin-13 alters the activation state of murine macrophages in vitro: comparison with interleukin-4 and interferon-gamma. Eur J Immunol 1994; 24: 1441–1445.

    Article  CAS  PubMed  Google Scholar 

  41. McBride WH, Economou JS, Nayersina R, Comora S, Essner R . Influences of interleukins 2 and 4 on tumor necrosis factor production by murine mononuclear phagocytes. Cancer Res 1990; 50: 2949–2952.

    CAS  PubMed  Google Scholar 

  42. Hart PH, Vitti GF, Burgess DR, Whitty GA, Piccoli DS, Hamilton JA . Potential antiinflammatory effects of interleukin 4: suppression of human monocyte tumor necrosis factor ca, interleukin 1, and prostaglandin E2. Proc Natl Acad Sci USA 1989; 86: 3803–3807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Trindade M, Nakashima Y, Lind M, Sun DH, Goodman SB, Maloney WJ et al. Interleukin-4 inhibits granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha expression by human monocytes in response to polymethylmethacrylate particle challenge in vitro. J Orthop Res 1999; 17: 797–802.

    Article  CAS  PubMed  Google Scholar 

  44. Arora S, Olszewski MA, Tsang TM, McDonald RA, Toews GB, Huffnagle GB . Effect of cytokine interplay on macrophage polarization during chronic pulmonary infection with Cryptococcus neoformans. Infect Immun 2011; 79: 1915–1926.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Rao AJ, Nich C, Dhulipala LS, Gibon E, Valladares R, Zwingenberger S et al. Local effect of IL-4 delivery on polyethylene particle induced osteolysis in the murine calvarium. J Biomed Mater Res A 2013; 101: 1926–1934.

    Article  CAS  PubMed  Google Scholar 

  46. Davies JQ, Gordon S . Isolation and culture of murine macrophages. Methods Mol Biol 2005; 290: 91–103.

    PubMed  Google Scholar 

  47. Stanley ER, Heard PM . Factors regulating macrophage production and growth. J Biol Chem 1977; 252: 4305–4312.

    CAS  PubMed  Google Scholar 

  48. Burgess AW, Metcalf D, Kozka IJ, Simpson RJ, Vairo G, Hamilton JA et al. Purification of two-forms of colony-stimulating factor from mouse L-cell conditioned medium. J Biol Chem 1985; 260: 16004–16011.

    CAS  PubMed  Google Scholar 

  49. Moura CC, Soares PB, de Souza MA, Zanetta-Barbosa D . Effect of titanium surface on secretion of IL1β and TGFβ1 by mononuclear cells. Braz Oral Res 2011; 25: 500–505.

    Article  PubMed  Google Scholar 

  50. Landis RC, Yagnik DR, Florey O, Philippidis P, Emons V, Mason JC et al. Safe disposal of inflammatory monosodium urate monohydrate crystals by differentiated macrophages. Arthritis Rhem 2002; 46: 3026–3033.

    Article  CAS  Google Scholar 

  51. Martin WJ, Shaw O, Liu X, Steiger S, Harper JL . Monosodium urate monohydrate crystal-recruited noninflammatory monocytes differentiate into M1-like proinflammatory macrophages in a peritoneal murine model of gout. Arthritis Rhem 2011; 63: 1322–1332.

    Article  CAS  Google Scholar 

  52. Pello OM, de Pizzol M, Soucek L, Zammataro L, Amabile A, Doni A et al. Role of c-MYC in alternative activation of human macrophages and tumor-associated macrophage biology. Blood 2012; 119: 411–421.

    Article  CAS  PubMed  Google Scholar 

  53. Weisser SB, McLarren KW, Kuroda E, Sly LM . Generation and characterization of murine alternatively activated macrophages. Methods Mol Biol 2013; 946: 225–239.

    Article  CAS  PubMed  Google Scholar 

  54. Allavena P, Chieppa M, Bianchi G, Solinas G, Fabbri M, Laskarin G et al. Engagement of the mannose receptor by tumoral mucins activates an immune suppressive phenotype in human tumor-associated macrophages. Clin Dev Immunol 2010; 2010: 547179.

    Article  CAS  PubMed  Google Scholar 

  55. Kigerl K, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG . Identification of distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration of the injured mouse spinal cord. J Neurosci 2009; 29: 13435–13444.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Tiju JW, Chen JS, Shun CT, Lin SJ, Liao YH, Chu CY et al. Tumor-associated macrophage-induced invasion and angiogenesis of human basal cell carcinoma cells by cyclooxygenase-2 induction. J Invest Dermatol 2009; 129: 1016–1025.

    Article  CAS  Google Scholar 

  57. Li CY, Chou TC, Wu CC, Wong CS, Ho ST, Yen MH et al. Dantrolene inhibits nitric oxide synthase in rat alveolar macrophages treated with lipopolysaccharide and interferon-gamma. Can J Anaesth 1998; 45: 246–252.

    Article  CAS  PubMed  Google Scholar 

  58. Fuentes-Duculan J, Suarez-Farinas M, Zaba LC, Nograles KE, Pierson KC, Mitsui H et al. A subpopulation of CD163 positive macrophages is classically activated in psoriasis. J Invest Dermatol 2010; 130: 2412–2422.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Lopez-Castejon G, Baroja-Mazo A, Pelegrin P . Novel macrophage polarization model: from gene expression to identification of new anti-inflammatory molecules. Cell Mol Life Sci 2011; 68: 3095–3107.

    Article  CAS  PubMed  Google Scholar 

  60. Livak KJ, Schmittgen TD . Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 2001; 25: 402–408.

    Article  CAS  PubMed  Google Scholar 

  61. Hirsch S, Austyn JM, Gordon S . Expression of the macrophage specific antigen F4/80 during differentiation of mouse bone marrow cells in culture. J Exp Med 1981; 154: 713–725.

    Article  CAS  PubMed  Google Scholar 

  62. Khazen W, M'Bika JP, Tomkiewicz C, Benelli C, Chany C, Achour A et al. Expression of macrophage-selective markers in human and rodent adipocytes. FEBS Lett 2005; 579: 5631–5634.

    Article  CAS  PubMed  Google Scholar 

  63. Keane TJ, Londono R, Turner N, Badylak SF . Consequences of ineffective decellularization of biologic scaffolds on the host response. Biomaterials 2012; 33: 1771–1781.

    Article  CAS  PubMed  Google Scholar 

  64. Brown BN, Londono R, Tottey S, Zhang L, Kukla KA, Wolf MT et al. Macrophage phenotype as a predictor of constructive remodeling following the implantation of biologically derived surgical mesh materials. Acta Biomater 2012; 8: 978–987.

    Article  CAS  PubMed  Google Scholar 

  65. Sicari BM, Johnson SA, Siu BF, Crapo PM, Daly KA, Jiang H et al. The effect of source animal age upon the in vivo remodeling characteristics of an extracellular matrix scaffold. Biomaterials 2012; 33: 5524–5533.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Benoit M, Barbarat B, Bernard A, Olive D, Mege JL . Coxiella burnetii, the agent of Q fever, stimulates an atypical M2 activation program in human macrophages. Eur J Immunol 2008; 38: 1065–1070.

    Article  CAS  PubMed  Google Scholar 

  67. Murphy BS, Sundareshan V, Cory TJ, Hayes D Jr, Anstead MI, Feola DJ . Azithromycin alters macrophage phenotype. J Antimicrob Chemother 2008; 61: 554–560.

    Article  CAS  PubMed  Google Scholar 

  68. Fiijsaka S, Usui I, Bukhari A, Ikutani M, Oya T, Kanatani Y et al. Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 2009; 58: 2574–2582.

    Article  CAS  Google Scholar 

  69. Roca H, Varsos ZS, Sud S, Craig MJ, Ying C, Pienta KJ . CCL2 and interleukin-6 promote survival of human CD11b peripheral blood mononuclear cells and induce M2-type macrophage polarization. J Biol Chem 2009; 49: 34342–34354.

    Article  CAS  Google Scholar 

  70. Choi KM, Kashyap PC, Dutta N, Stoltz GJ, Ordog T, Shea Donohue T et al. CD206-positive M2 macrophages that express heme oxygenase-1 protect against diabetic gastroparesis in mice. Gastroenterology 2010; 138: 2399–2409.

    Article  CAS  PubMed  Google Scholar 

  71. Aron-Wisnewsky J, Tordjman J, Poitou C, Darakhshan F, Hugol D, Basdevant A et al. Human adipose tissue macrophages: M1 and M2 cell surface markers in subcutaneous and omental depots and after weight loss. J Clin Endocrinol Metab 2009; 94: 4619–4623.

    Article  CAS  PubMed  Google Scholar 

  72. Stein M, Keshav S, Harris N, Gordon S . Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J Exp Med 1992; 176: 287–292.

    Article  CAS  PubMed  Google Scholar 

  73. Lolmede K, Campana L, Vezzoli M, Bosurgi L, Tonlorenzi R, Clementi E et al. Inflammatory and alternatively activated human macrophages attract vessel-associated stem cells, relying on separate HMGB1- and MMP-9-dependent pathways. J Leukoc Biol 2009; 85: 779–787.

    Article  CAS  PubMed  Google Scholar 

  74. Lumeng CN, Bodzin JL, Saltiel AR . Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 2007; 117: 175–184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Beutler BA, Milsark IW, Cerami A . Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo. J Immunol 1985; 135: 3972–3977.

    CAS  PubMed  Google Scholar 

  76. Yamshchikov VF, Mishina M, Cominelli F . A possible role of IL-1ra 3′-untranslated region in modulation of protein production. Cytokine 2002; 10: 897–903.

    Google Scholar 

  77. van Deuren M, Twickler TB, de Waal Malefyt MC, van Beem H, van der Ven-Jongekrijg J, Verschueren CM et al. Elective orthopedic surgery, a model for the study of cytokine activation and regulation. Cytokine 1998; 17: 98–107.

    Google Scholar 

  78. Duvel A, Frank C, Schnapper A, Schuberth HJ, Sipka A . Classically or alternatively activated bovine monocyte-derived macrophages in vitro do not resemble CD163/Calprotectin biased macrophage populations in the teat. Innate Immunity 2012; 18: 886–896.

    Article  CAS  PubMed  Google Scholar 

  79. Daigneault M, Preston JA, Marriott HM, Whyte MK, Dockrell DH . The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages. PLoS ONE 2010; 5: e8668.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Xia W, Hilenbrink AR, Matteson EL, Lockwood MB, Cheng JX, Low PS . A functional folate receptor is induced during macrophage activation and can be used to target drugs to activated macrophages. Blood 2009; 113: 438–446.

    Article  CAS  PubMed  Google Scholar 

  81. Zhang L, Tizard IR . Activation of amouse macrophage cell line by acemannan: the major carbohydrate fraction from Aloe vera gel. Immunopharm 1996; 35: 119–128.

    Article  CAS  Google Scholar 

  82. Kolodziejska KE, Burns AR, Moore RH, Stenoien DL, Eissa NT . Regulation of inducible nitric oxide synthase by aggresome formation. Proc Natl Acad Sci USA 2005; 102: 4854–4859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Jones RJ, Jourd'heuil D, Salerno JC, Smith SM, Singer HA . iNOS regulation by calcium/calmodulin-dependent protein kinase II in vascular smooth muscle. Am J Physiol Heart Circ Physiol 2007; 292: H2634–H2642.

    Article  CAS  PubMed  Google Scholar 

  84. Pandil L, Kolodziejska KE, Zeng S, Eissa NT . The physiologic aggresome mediates cellular inactivation of iNOS. Proc Natl Acad Sci USA 2009; 106: 1211–1215.

    Article  Google Scholar 

  85. Zhou J, Tsai YT, Weng H, Baker DW, Tang L . Real time monitoring of biomaterial-mediated inflammatory responses via macrophage-targeting NIR nanoprobes. Biomaterials 2011; 32: 9383–9390.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Zhou J, Tsai YT, Weng H, Tang L . Noninvasive assessment of localized inflammatory responses. Free Radic Biol Med 2012; 52: 218–226.

    Article  CAS  PubMed  Google Scholar 

  87. Zhou J, Tsai YT, Weng H, Tang EN, Nair A, Dave DP et al. Real-time detection of implant-associated neutrophil responses using a formyl peptide receptor-targeting NIR nanoprobe. Int J Nanomed 2012; 7: 2057–2068.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank Dr Alexander Harris of Stanford University for assistance in the statistical analysis. We would also like to thank Dr Stephen Badylak and Brian Sicari for assistance in choosing appropriate macrophage markers. This work was supported by NIH grants 2R01AR055650-05 and 1R01AR063717-01; the Ellenburg Chair in Surgery at Stanford University; and the Stanford Medical Scholars Program.

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Orthopaedic Research Laboratories, Stanford University School of Medicine, Stanford, CA, USA

    Joseph K Antonios, Zhenyu Yao, Chenguang Li, Allison J Rao & Stuart B Goodman

Authors
  1. Joseph K Antonios
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhenyu Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chenguang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Allison J Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Stuart B Goodman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stuart B Goodman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Antonios, J., Yao, Z., Li, C. et al. Macrophage polarization in response to wear particles in vitro. Cell Mol Immunol 10, 471–482 (2013). https://doi.org/10.1038/cmi.2013.39

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2013.39

Keywords

This article is cited by

Search

Advanced search

Quick links