RESPONSE OF 3 MURINE MACROPHAGE POPULATIONS TO PARTICULATE DEBRIS - BONE-RESORPTION IN ORGAN-CULTURES

Particulate wear debris from bone cement or prosthetic components can stimulate macrophages to cause bone resorption. We compared the effect of particle composition (titanium and polymethylmethacrylate as inherent components of prosthetic materials or bone cement and polystyrene as a reference material) on the secretion of interleukin-1 and prostaglandin E(2) by peritoneal macrophages and monocyte/macrophage cell lines (P388D(1) and IC-21) and on the bone-resorbing activity of conditioned medium harvested from these particle-challenged macrophages. Titanium particles (1-3 mu m) in peritoneal macrophage cultures exhibited significantly enhanced bone-resorbing activity measured as Ca-45 release, whereas polymethylmethacrylate and polystyrene exhibited this effect to a greater extent in the P388D(1) and IC-21 monocyte/macrophage cultures. Although exogenous prostaglandin E(2) and recombinant human interleukin-1 could significantly increase the Ca-45 release and indomethacin significantly reduced both the spontaneous calcium efflux and active Ca-45 release from calvarial bones labeled in vivo, the levels of interleukin-1 and prostaglandin E(2), alone or together, did not always correlate with the bone-resorbing activity of conditioned media. Thus, the actual levels of potent bone-resorbing agents (prostaglandin E(2) and interleukin-1) measured in conditioned tissue culture media did not necessarily reflect the bone-resorbing capability. An important result of this study is that different macrophage populations may respond differently to the same microenvironmental signal, which in our investigation was particulate wear debris of differing composition and size.