Alternative macrophage activation in periprosthetic osteolysis

Abstract

Several disorders characterized by macrophages accumulating non-disposable (or hard to dispose of) material or formation of multinucleated giant cell containing granulomas have been linked to elicitation of an alternative macrophage activation phenotype. Gene profiling efforts have shown that alternative macrophage activation can exist in numerous forms, each specific for the particular biological niche in which the macrophage finds itself, accentuating the plasticity of this cell type. Periprosthetic osteolysis is characterized by macrophage phagocytosis of particles of wear debris and formation of foreign body granulomas, suggesting the hypothesis that it may represent a new member of this group of diseases characterized by alternative macrophage activation. Gene profiling has provided strong supportive evidence for this hypothesis, revealing that periprosthetic tissues of osteolysis patients show the presence of a pronounced alternative macrophage activation pathway, with the classical pro-inflammatory activation pathway being less evident. These findings have important implications for our understanding of periprosthetic osteolysis and how to approach future investigations into this disease.