Nitric oxide release by macrophages in response to particulate wear debris

At the interface between a prosthetic implant and bone, macrophage interaction with particulate wear debris is a key event in the initiation of localized bone resorption, leading to aseptic loosening of the prostheses. Numerous investigators have reported that macrophages release a variety of cytokines and mediators including tumor necrosis factor, interleukin-1, prostaglandin E2, and interleukin-6 when they are stimulated with particulate wear debris. In this study, we have demonstrated that macrophages stimulated with particulate debris are also capable of releasing in copious amounts a key inflammatory chemical, nitric oxide. This release of nitric oxide was dependent upon the period of culture and the type and dosage of the challenging particles. Titanium-alloy particles were the most stimulatory, followed by commercially pure titanium and polymethyl-methacrylate. While the role of nitric oxide in osteolysis is not clearly understood, the literature suggests that it may be a key mediator in inhibiting DNA synthesis, in cell proliferation, and in stimulating PGE2 release. This finding enhances our understanding of the sequence of events occurring at the bone-implant interface during wear debris-mediated osteolysis, and exposes potential avenues to interrupt this sequence.