Induction of macrophage apoptosis by ceramic and poly-ethylene particles in vitro

The purpose of this study was to investigate in vitro the presence of apopt otic cell death after macrophage stimulation with different ceramic (Al2O3 and ZrO2) and high density polyethylene (HDP) particles. We also analyzed t he effects of particle size, concentration, and composition. The J774 mouse macrophage cell line was exposed to commercial particles of different size s (up to 4.5 mu m) and concentrations (up to 500 particles per macrophage). Fluorescence microscopy and DNA laddering were used to investigate the pre sence of apoptosis in cell cultures after 24 h of incubation. Fluorescence microscopy of propidium iodide stained cells showed two characteristic morp hological features that occur in apoptotic cells, namely nuclear condensati on and heterogeneity of stain uptake. The effect of ceramic particles on ap optotic nuclear morphology was size- and concentration-dependent and reache d a plateau above 150 particles per macrophage at 1.3 mu m. With regards to composition, we did not find any difference in cell morphology between Al2 O3 and ZrO2. Ceramic and HDP particles induced DNA fragmentation into oligo nucleosomes as evidenced by DNA laddering, another characteristic of apopto sis. The induction of DNA laddering was size- and concentration-dependent w hereas particle composition (Al2O3 vs. ZrO2 and Al2O3 vs. HDP) had no effec t. In conclusion our results demonstrated that ceramic and HDP particles in duce macrophage apoptotic cell death in vitro and open doors for possible m odulation of debris-induced periprosthetic osteolysis. (C) 1999 Elsevier Sc ience Ltd. All rights reserved.