title: In vitro macrophage response to nanometer-size chromium oxide particles.
abstract: An increasing number of studies have reported adverse tissue reactions around metal-on-metal (MM) hip implants. However, the origin and mechanisms of these reactions remain unclear. Moreover, the biological effects of nanometer-size chromium oxide particles, the predominant type of wear particles produced by MM implants, remain mostly unknown. The purpose of this study was to analyze the cytotoxic effects of clinically relevant nanometer-size chromium oxide particles on macrophage response in vitro. J774.A1 macrophages were cultured with either 60 nm or 700 nm commercially available Cr2 O3 particles at different concentrations. Two different particle sizes were analyzed to evaluate potential volume effects. Cell mortality was analyzed by light microscopy, flow cytometry (annexin V-fluorescein isothiocyanate and propidium iodide assay), and using a cell death detection enzyme-linked immunosorbant assay (ELISA). Tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1 alpha (MIP-1α) release was measured by ELISA, and gene expression was analyzed by quantitative real-time PCR. Results showed that, at high concentrations, Cr2 O3 particles of both sizes can be cytotoxic, inducing significant decreases in total cell numbers and increases in necrosis. Results also suggested that these effects were dependent on particle volume. However, TNF-α, MCP-1, and MIP-1α cytokine release and gene expression remained low. Overall, this study demonstrates that nanometer-size particles of Cr2 O3 , a stable form of chromium oxide ceramic, have rather low cytotoxic effects on macrophages. Therefore, these particles may not be the main culprit in the initiation of the inflammatory reaction in MM periprosthetic tissues. However, other parameters (e.g., potential intracellular damage) remain to be investigated.
authors.affiliation: Department of Mechanical Engineering, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
authors.forename: Robilyn
authors.initials: R
authors.lastname: VanOs
authors.forename: Levannia L
authors.initials: LL
authors.lastname: Lildhar
authors.forename: Eric A
authors.initials: EA
authors.lastname: Lehoux
authors.forename: Paul E
authors.initials: PE
authors.lastname: Beaulé
authors.forename: Isabelle
authors.initials: I
authors.lastname: Catelas
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry / Q000633:toxicity*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism; D017608:Chromium Compounds / Q000737:chemistry / Q000633:toxicity*; D019544:Equipment Failure Analysis; D015870:Gene Expression / Q000187:drug effects; D006622:Hip Prosthesis / Q000009:adverse effects; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects* / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity* / Q000648:ultrastructure; D051379:Mice; D009336:Necrosis; D010316:Particle Size; D011475:Prosthesis Failure; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; C491768:Ccl2 protein, mouse; C496534:Ccl3 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D017608:Chromium Compounds; D014409:Tumor Necrosis Factor-alpha; C023600:chromic oxide
keywords: chromium oxide; cytotoxicity; hip implants; macrophages; wear particles