Effects of cobalt and chromium ions on lymphocyte migration

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Abstract

A T cell-mediated hypersensitivity reaction has been reported in some patients with CoCrMo-based implants. However, the role of cobalt and chromium ions in this reaction remains unclear. The objective of the present study was to analyze the effects of Co2+ and Cr3+ in culture medium, as well as the effects of culture supernatants of macrophages exposed to Co2+ or Cr3+, on the migration of lymphocytes. The release of cytokines/chemokines by macrophages exposed to Co2+ and Cr3+ was also analyzed. The migration of murine lymphocytes was quantified using the Boyden chamber assay and flow cytometry, while cytokine/chemokine release by J774A.1 macrophages was measured by ELISA. Results showed an ion concentration-dependent increase in TNF-α and MIP-1α release and a decrease in MCP-1 and RANTES release. Migration analysis showed that the presence of Co2+ (8 ppm) and Cr3+ (100 ppm) in culture medium increased the migration of T lymphocytes, while it had little or no effect on the migration of B lymphocytes, suggesting that Co2+ and Cr3+ can stimulate the migration of T but not B lymphocytes. Levels of T lymphocyte migration in culture medium containing Co2+ or Cr3+ were not statistically different from those in culture supernatants of macrophages exposed to Co2+ or Cr3+, suggesting that the effects of the ions and chemokines were not additive, possibly because of ion interference with the chemokines and/or their cognate receptors. Overall, results suggest that Co2+ and Cr3+ are capable of stimulating the migration of T (but not B) lymphocytes in the absence of cytokines/chemokines, and could thereby contribute to the accumulation of more T than B lymphocytes in periprosthetic tissues of some patients with CoCrMo-based implants. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

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