title: Macrophage/particle interactions: effect of size, composition and surface area.
abstract: Particulate wear-debris are detected in histiocytes/macrophages of granulomatous tissues adjacent to loose joint prostheses. Such cell-particle interactions have been simulated in vitro by challenging macrophages with particles dosed according to weight percent, volume percent, and number of particles. Each of these dosage methods has inherent shortcomings due to varying size and density of challenging particles of different compositions. In this study we challenged P388D1 macrophages with titania and polystyrene particles (< 2 microns), with dosage based on the ratio of the surface area of the particles to the surface area of the cells. The effect of size and composition on (1) the bone resorbing activity, (2) fibroblast proliferation, and (3) secretion of IL-1 and PGE2 was determined. Macrophage response to particulate debris appears to be dependent on particle size, composition, and dose as given by surface area ratio. P388D1 macrophages challenged with titania particles released IL-1, but did not stimulate fibroblasts. Inhibition of macrophage DNA synthesis at higher surface area ratios suggests cell damage or death. Particle-stimulated cells increased bone resorption up to 125% of controls but released only basal levels of PGE2. Macrophages stimulated by wear particles are expected to synthesize numerous factors affecting events in the bone-implant interface. Using the concept of surface area ratio allows us to study and compare such cellular responses to wear particles in a standardized manner.
authors.affiliation: Department of Orthopedic Surgery, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612.
authors.forename: A S
authors.initials: AS
authors.lastname: Shanbhag
authors.forename: J J
authors.initials: JJ
authors.lastname: Jacobs
authors.forename: J
authors.initials: J
authors.lastname: Black
authors.forename: J O
authors.initials: JO
authors.lastname: Galante
authors.forename: T T
authors.initials: TT
authors.lastname: Glant
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001862:Bone Resorption / Q000139:chemically induced; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D015232:Dinoprostone / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D007375:Interleukin-1 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D010587:Phagocytosis; D011137:Polystyrenes / Q000494:pharmacology; D013499:Surface Properties; D014025:Titanium / Q000494:pharmacology
chemical_list: D001672:Biocompatible Materials; D017077:Culture Media, Conditioned; D007375:Interleukin-1; D011137:Polystyrenes; C009495:titanium dioxide; D004247:DNA; D014025:Titanium; D015232:Dinoprostone; D002118:Calcium