Low dose metal particles can induce monocyte/macrophage survival

Aseptic loosening results in pain, loss of function, and ultimately prosthetic joint failure and revision surgery. The generation of wear particles from the prosthesis is a major factor in local osteolysis. We investigated the effects of such wear particles on the survival of monocytes and macrophages, populations implicated in wear particle-driven pathology. Particles from titanium aluminum vanadium (TiAlV) and cobalt chromium (CoCr) alloys were generated in-house and were equivalent in size (0.5-3 microm) to those seen in patients. Human CD14(+) monocytes and murine bone marrow-derived macrophages (BMM) were treated with TiAlV and CoCr particles in vitro, and cell survival was assayed. Both particles increased monocyte and macrophage survival in a dose-dependent manner, with an optimal concentration of around 10(7) particles/mL. Conditioned media from particle-treated BMM also increased macrophage survival. Studies with antibody blockade and gene-deficient mice suggest that particle-induced BMM survival is independent of endogenous CSF-1 (M-CSF), GM-CSF, and TNFalpha. These data indicate that wear particles can promote monocyte/macrophage survival in vitro possibly via an endogenous mediator. If this phenomenon occurs in vivo, it could mean that increased numbers of macrophages (and osteoclasts) would be found at a site of joint implant failure, which could contribute to the local inflammatory reaction and osteolysis.