Evaluation of the response of primary human peripheral blood mononuclear phagocytes to challenge within vitro generated clinically relevant UHMWPE particles of known size and dose

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Abstract
The response of primary human peripheral blood mononuclear phagocytes to challenge with clinically relevant ultra-high molecular weight polyethylene (UHMWPE) wear debris of known particle size and dose was evaluated. Particles with a mean size of 0.24, 0.45, 1.7, 7.6, and 88 μm were cocultured with cells for 24 h before assessment of cell viability and production of the osteolytic cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and granulocyte macrophage colony-stimulating factor, and prostaglandin E2. All particle fractions were evaluated at particle volume (μm3) to cell number ratios of 10:1 and 100:1, which had been previously identified as being the most stimulatory and clinically relevant. None of the test fractions had an effect on cell viability. Whereas the heterogeneity of human individuals was clearly evident in the responses of the donors evaluated in this study (the response of donor 3 was between 5 and 20 times greater than the other donors), the most biologically active particles were found to be submicrometer in size. Stimulation with phagocytosable particles (0.24, 0.45, and 1.7 μm) resulted in enhanced levels of cytokine secretion. Macrophages stimulated with particles outside this size range produced considerably less cytokines at the volumes tested. These results confirm earlier findings and suggest that the size and volume of UHMWPE particles are critical factors in macrophage activation. Furthermore, they suggest that the heterogeneity of human individuals may be another important factor in determining implant life. © 2000 John Wiley & Sons, Inc. J Biomed Mater Res, 52, 296–307, 2000.