Exposure of polyethylene particles induces interferon-γ expression in a natural killer T lymphocyte and dendritic cell coculture systemin 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); co-culture 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 co-culture 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 Interferon-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 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.

Periprosthetic UHMWPE Wear Debris Induces Inflammation, Vascularization, and Innervation After Total Disc Replacement in the Lumbar Spine

“…Specifically, activated macrophages have been reported to contribute to experimental pain states by releasing factors such as TNFa, IL-1b, IL-8, NGF, nitric oxide, and prostanoids [22,33,37]. In the context of periprosthetic wear debris, joint arthroplasty studies revealed that UHMWPE particles can activate both fibroblasts and macrophages to secrete TNFa and IL-1ß, which can synergistically contribute to the recruitment of more macrophages [19,32]. Accordingly, our previous work showed an increased infiltration of macrophages in TDR tissues containing wear particles [41], and this study confirmed that macrophages (and fibroblasts) produced factors that are known to mediate direct or indirect pain.…”

Immune response and innervation signatures in aseptic hip implant loosening

“…Despite reported not toxic as metallic particles or studied as polymeric debris [ 12 , 33 , 34 ], ZrO 2 particles should not be neglected, as they are numerous, common and nano-sized with potential to unbalance inflammation towards osteolysis. It has been reported that particle-induced response is prone to drive macrophages towards M1 phenotype and that M1:M2 ratio was higher in synovial membrane-like interface tissue than in OA synovial tissues [ 35 , 36 ]. However, macrophage polarization in joint tissues remains controversial.…”

The Impact of Metal Ion Exposure on the Cellular Behavior of Human Osteoblasts and PBMCs: In Vitro Analyses of Osteolytic Processes

“…While wear products do not only induce a local response but also a systemic one [ 16 ], more complex cell culture models have to be established to understand the different interactions of cells. Up to now, there are only a few published studies dealing with co-culture cell models for analysing osteolytic processes in response to wear particles [ 17 , 18 , 19 , 20 , 21 ]. Therefore, we intended to establish the co-culture of human osteoblasts and PBMCs to analyse the impact of cellular interactions in response to metal ion exposure compared to single cell culture experiments.…”