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 Co(2+) ions released in the peri-prosthetic tissue by the wear of MM THA. The toxicity of Co(2+) is still debated, but Co(2+) is a potential inhibitor of the Hv1 proton channel that sustains the production of superoxide by neutrophils. In this study, we show that the Co(2+) concentration in peri-prosthetic tissue from patients with MM THA averages 53 μM and that such high concentrations of Co(2+) alter the antibacterial activity of human neutrophils in vitro by inhibiting Hv1 proton channels. We show that submillimolar concentrations of Co(2+) inhibit proton currents, impair the extrusion of cytosolic acid, and decrease the production of superoxide in human neutrophils. As a result, Co(2+) 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 Co(2+). By inhibiting proton channels, the Co(2+) ions released by metal prostheses might therefore promote bacterial infections in patients with metal-on-metal total hip arthroplasty.
Department of Cell Physiology and Metabolism, University of Geneva, 1 rue Michel-Servet CH-1211 Geneva 4, Switzerland.
Samira
S
Daou
Antoun
A
El Chemaly
Panayiotis
P
Christofilopoulos
Louis
L
Bernard
Pierre
P
Hoffmeyer
Nicolas
N
Demaurex
D002478:Cells, Cultured; D003035:Cobalt / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects*; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects*; D019736:Prostheses and Implants / Q000009:adverse effects; D017382:Reactive Oxygen Species / Q000378:metabolism
D007473:Ion Channels; D017382:Reactive Oxygen Species; D003035:Cobalt; D019255:NADPH Oxidases