title: Exposure of polyethylene particles induces interferon-γ expression in a natural killer T lymphocyte and dendritic cell coculture system in vitro: a preliminary study.
abstract: Two major issues in total joint arthroplasty are loosening of implants and osteolysis caused by wear particle-induced inflammation. Wear particles stimulate the release of pro-inflammatory cytokines, chemokines, and other inflammatory mediators from macrophages and other cells. Although the biological response of macrophages to wear debris is well established, the role of other cell types such as natural killer T lymphocytes (NKT) and dendritic cells (DCs) is limited. Here we show that ultra-high molecular weight polyethylene (UHMWPE) particles stimulate NKT cells to secrete Interferon-γ (IFN-γ); coculture with DCs further enhanced IFN-γ secretion. Furthermore, UHMWPE particles did not stimulate NKT cells to secrete IL-4, while the NKT cell natural ligand α-galactosylceramide (α-GalCer) treatment in the coculture system significantly enhanced both IFN-γ and IL-4 expression by NKT cells. Comparatively, NKT cells and/or DCs exposed to polymethylmethacrylate particles did not stimulate IFN-γ or IL-4 expression. Mouse bone marrow derived macrophage polarization by lipopolysaccharide and conditioned medium from NKT cells and/or DCs exposed to UHMWPE particles increased tumor necrosis factor-α (TNF-α), but reduced arginase-1 expression in macrophages. The current findings indicate that UHMWPE particles stimulate NKT cells/DCs to produce pro-inflammatory cytokines; this pathway is a novel therapeutic target to mitigate wear particle induced peri-prosthetic osteolysis.
authors.affiliation: Department of Orthopaedic Surgery, Stanford University, Stanford, California.
authors.forename: Tzu-Hua
authors.initials: TH
authors.lastname: Lin
authors.forename: Sunny
authors.initials: S
authors.lastname: Kao
authors.forename: Taishi
authors.initials: T
authors.lastname: Sato
authors.forename: Jukka
authors.initials: J
authors.lastname: Pajarinen
authors.forename: Ruth
authors.initials: R
authors.lastname: Zhang
authors.forename: Florence
authors.initials: F
authors.lastname: Loi
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yao
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011095:Polyethylenes / Q000494:pharmacology*; D016133:Polymerase Chain Reaction
chemical_list: D011095:Polyethylenes; C111601:ultra-high molecular weight polyethylene; D007371:Interferon-gamma
keywords: Natural killer T lymphocytes; UHMWPE; dendritic cells; periprosthetic osteolysis; wear particles