Macrophage exposure to polymethyl methacrylate leads to mediator release and injury

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.