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.

Clodronate prevents prosthetic migration: A randomized radiostereometric study of 50 total knee patients

“…Once a membrane is established and an implant is unstable, the situation seems to be very different. Fluid pressure generated by instability has a strong osteolysis-activating effect , and there is also some evidence that wear particles entering the membrane may activate osteoclasts (Horowitz et al 1991, Kadoya et al 1997. Finally, increasing fatigue may be an alternative explanation of continuous migration (Taylor and Tanner 1997).…”

“…Once primary stability is lost and a fibrous membrane formed, micromotion will prevent osseous anchorage from being reestablished. The membrane that ensues may then allow further osteolysis with time, due to fluid pressure effects (Robertsson et al 1997 or possibly effects from particles entering the membrane (Horowitz et al 1991, Kadoya et al 1997. These secondary phenomena may lead to clinical loosening.…”

Kinetics of polymethylmethacrylate particle‐induced inhibition of osteoprogenitor differentiation and proliferation

“…The absence of these cells in particle-treated cultures indicates that PMMA particles do not induce adherent monocytes to differentiate into macrophages and osteoclasts. Because osteogenic cultures that are not challenged with particles still contain monocyte-macrophages, the absence of these cells in particletreated cultures is most likely due to a cytotoxic effect of PMMA particles 20,21 and not to a physiologic effect of the osteogenic medium. Together, these results demonstrate that the inhibition of osteoprogenitor differentiation is unlikely to be due to inhibitory factors released by particle-activated cells in the heterogeneous bone marrow cell culture.…”

Wear debris from two different alumina-on-alumina total hip arthroplasties

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14] Various studies have shown the good performance of the alumina ceramic-on-ceramic articular surfaces in terms of frictional behaviour, low annual rates of wear and relatively low reactivity of debris in the periprosthetic tissues, compared with polyethylene wear from metal-polyethylene couples. [15][16][17][18][19][20][21][22][23] Light-microscope studies of membranes around revised ceramic THRs reported sizes of alumina particle of between 1 and 3 m which is similar to the grain size of alumina used for production.…”