Soluble and particulate Co‐Cr‐Mo alloy implant metals activate the inflammasome danger signaling pathway in human macrophages: A novel mechanism for implant debris reactivity
- 22 December 2008
- journal article
- Published by Wiley in Journal of Orthopaedic Research
- Vol. 27 (7), 847-854
- https://doi.org/10.1002/jor.20826
Abstract
Immune reactivity to soluble and particulate implant debris remains the primary cause of aseptic inflammation and implant loosening. However, the intracellular mechanisms that trigger immune cells to sense and respond to exogenous nonbiological agents such as metal particles or metal ions released from orthopedic implants remain unknown. Recent studies in immunology have outlined the importance of the intracellular inflammasome complex of proteins in sensing danger/stress signals triggered by nonbiological agents in the cytosol of macrophages. We hypothesized that metal implant debris can activate the inflammasome pathway in macrophages that causes caspase‐1‐induced cleavage of intracellular pro‐IL‐1β into its mature form, resulting in IL‐1β secretion and induction of a broader proinflammatory response. We tested this hypothesis by examining whether soluble cobalt, chromium, molybdenum, and nickel ions and Co‐Cr‐Mo alloy particles induce inflammasome‐ mediated macrophage reactivity. Our results demonstrate that these agents stimulate IL‐1β secretion in human macrophages that is inflammasome mediated (i.e., NADPH‐, caspase‐1‐, Nalp3‐, and ASC‐dependent). Thus, metal ion‐ and particle‐induced activation of the inflammasome in human macrophages provides evidence of a novel pathway of implant debris‐induced inflammation, where contact with implant debris is sensed and transduced by macrophages into a proinflammatory response. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 847–854, 2009Funding Information
- NIH/NIAMS (PAR 99-099, PA 01-141-099)
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