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Macrophage exposure to polymethyl methacrylate leads to mediator release and injury
S M Horowitz1, T L Gautsch, C G Frondoza
1Department of Orthopaedic Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Abstract:
To understand further the role of macrophages in the loosening of cemented arthroplasty, several in vitro effects of polymethyl methacrylate (PMMA) particle exposure in these cells were studied. The kinetics of arachidonic acid and derived inflammatory mediator release was characterized following macrophage exposure to either PMMA or control polystyrene particles. Temporal release of radiolabeled products by [14C]arachidonate-labeled cells was determined by sequential scintillation counting. Significant dose-dependent release of arachidonic acid mediators by macrophages was observed within half an hour of exposure to either PMMA or styrene particles. Unexposed control cells incubated in media alone did not release detectable amounts of radiolabeled products. The leakage of intracellular lactate dehydrogenase (LDH), a marker of cell injury, was detected spectrophotometrically 4 h following exposure to PMMA but not styrene. PMMA-induced LDH release was dose dependent. In contrast, polystyrene exposure failed to increase LDH release above unexposed control cells. These in vitro studies reveal that macrophages rapidly released arachidonic acid and derived inflammatory mediators in response to both PMMA and styrene particles. However, cells exposed to PMMA are lethally damaged, as reflected by the subsequent leakage of their intracellular LDH. We propose that a similar sequence of events may occur when macrophages encounter PMMA particles at the bone-cement interface. This is characteristic of a foreign body granulomatous response.
Insights
Macrophages exposed to polymethyl methacrylate (PMMA) particles rapidly release inflammatory mediators and suffer cell damage. This suggests PMMA particles contribute to implant loosening via a foreign body granulomatous response.
Area of Science:
- Biomaterials Science
- Immunology
- Orthopedic Surgery
Background:
- Loosening of cemented arthroplasty is a significant clinical challenge.
- Macrophages play a critical role in the foreign body response to implant debris.
Purpose of the Study:
- To investigate the in vitro effects of polymethyl methacrylate (PMMA) particles on macrophages.
- To elucidate the role of macrophage-derived inflammatory mediators in implant loosening.
Main Methods:
- Macrophages were exposed to PMMA or polystyrene particles in vitro.
- Release of arachidonic acid and inflammatory mediators was quantified using radiolabeling and scintillation counting.
- Cellular injury was assessed by measuring lactate dehydrogenase (LDH) leakage.
Main Results:
- Both PMMA and polystyrene particles induced rapid, dose-dependent release of arachidonic acid mediators from macrophages.
- PMMA particle exposure led to significant, dose-dependent lactate dehydrogenase (LDH) release, indicating cell death.
- Polystyrene particles did not cause significant LDH release.
Conclusions:
- Macrophages rapidly release inflammatory mediators in response to PMMA particles.
- PMMA particles cause lethal damage to macrophages, contributing to the foreign body granulomatous response at the bone-cement interface.
- This mechanism likely contributes to the loosening of cemented arthroplasty.