title: Low dose metal particles can induce monocyte/macrophage survival.
abstract: 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.
authors.affiliation: The University of Melbourne, Cooperative Research Centre for Chronic Inflammatory Disease, Royal Melbourne Hospital, Parkville, Vic. 3050 Australia. dlacey@unimelb.edu.au
authors.forename: Derek C
authors.initials: DC
authors.lastname: Lacey
authors.forename: Bernard
authors.initials: B
authors.lastname: De Kok
authors.forename: Felix I
authors.initials: FI
authors.lastname: Clanchy
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Bailey
authors.forename: Kathy
authors.initials: K
authors.lastname: Speed
authors.forename: David
authors.initials: D
authors.lastname: Haynes
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Graves
authors.forename: John A
authors.initials: JA
authors.lastname: Hamilton
mesh_terms: D000497:Alloys; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002858:Chromium Alloys / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology; D008670:Metals / Q000494:pharmacology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000473:pathology; D010014:Osteolysis / Q000209:etiology / Q000473:pathology; D014025:Titanium / Q000494:pharmacology
chemical_list: D000497:Alloys; D002858:Chromium Alloys; D017077:Culture Media, Conditioned; D008670:Metals; C031462:titanium alloy (TiAl6V4); D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D014025:Titanium