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INTERNALIZATION OF METAL PARTICLES AND IONS BY MACROPHAGES IN VITRO



Abstract

Metal particles and ions are liberated from the articular interface of metal-metal (MM) total hip arthroplasties. To better understand their cellular effect, we analyzed the internalization of these metal particles and ions by macrophages in vitro. Macrophages were exposed to metal particles isolated from MM prostheses cycled in a hip simulator and to metal ions. Cells were processed for transmission electron microscopy analysis. Results reveal the internalization of metal particles and Cr3+ ions in specifically localized cytoplasmic areas. This study is the first to reveal that metal particles of clinically relevant size and Cr3+ ions are internalized by an apparently active process.

In order to minimize articular interface wear, metal-metal (MM) hip implants have been considered as an alternative to conventional metal-polyethylene bearings. While the local histological effects of the metallic particles and ions appear to be similar to that seen with metal-polyethylene hip replacements (i.e., a foreign-body macrophage response), little is known about the cellular effects of these metal particles and ions.

The purpose of this study was to better understand the cellular effect of metal particles and ions, we analyzed their internalization by macrophages in vitro.

J774 mouse macrophages were exposed to metal particles isolated from serum of MM prostheses cycled in a hip simulator and to Cr3+ (CrCl3) and Co2+ (CoCl2) ions. Cells were then processed for transmission electron microscopy analysis.

Micrographs revealed the internalization of metal particles and Cr3+ ions in specifically localized cytoplasmic areas, suggesting that they are phagocytosed via an active pathway. Energy disperse X-ray analysis spectra of macrophages incubated with Cr3+ revealed a chromium phosphate composition. The same structure and composition were also observed when Cr3+ ions were incubated in culture medium without cells, suggesting that they were formed outside the cells. Co2+ ions did not form visibly agglomerated structures.

This study is the first to reveal that metal particles of clinically relevant size are internalized by an apparently active process and that Cr3+ ions can be internalized by macrophages after binding to phosphorus or phosphoproteins. Kinetic studies are now necessary to better understand the mechanism of phagocytosis and the ultimate outcome of these particles and ions in macrophages.

Correspondence should be addressed to Cynthia Vezina, Communications Manager, COA, 4150-360 Ste. Catherine St. West, Westmount, QC H3Z 2Y5, Canada