期刊
BIOMATERIALS
卷 32, 期 7, 页码 1769-1777出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2010.11.016
关键词
Proton channels; Phagocytosis; NADPH oxidase; Bacterial killing; Innate immunity
资金
- Swiss National Science Foundation [3100A0-118393]
- ENDO-Stiftung, Hamburg, Germany
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 pen-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 than the Co2+ concentration in pen-prosthetic tissue from patients with MM THA averages 53 mu M 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 mu M 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. (C) 2010 Elsevier Ltd. All rights reserved.
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