The potential role of cobalt ions released from metal prosthesis on the inhibition of Hv1 proton channels and the decrease in Staphyloccocus epidermidis killing by human neutrophils

Infection by Staphylococcus epidermidis is a devastating complication of metal-on-metal (MM) total hip arthroplasty (THA). Neutrophils are the first line of defense against infection, and these innate immune cells are potentially exposed to Co2+ ions released in the peri-prosthetic tissue by the wear of MM THA. The toxicity of Co2+ is still debated, but Co2+ is a potential inhibitor of the Hv1 proton channel that sustains the production of superoxide by neutrophils. In this study, we show that the Co2+ concentration in peri-prosthetic tissue from patients with MM THA averages 53 μM and that such high concentrations of Co2+ alter the antibacterial activity of human neutrophils in vitro by inhibiting Hv1 proton channels. We show that submillimolar concentrations of Co2+ inhibit proton currents, impair the extrusion of cytosolic acid, and decrease the production of superoxide in human neutrophils. As a result, Co2+ reduces the ability of human neutrophils to kill two strains of Staphyloccocus epidermidis by up to 7-fold at the maximal concentration tested of 100 μM Co2+. By inhibiting proton channels, the Co2+ ions released by metal prostheses might therefore promote bacterial infections in patients with metal-on-metal total hip arthroplasty.