title: Surveillance of systemic trafficking of macrophages induced by UHMWPE particles in nude mice by noninvasive imaging.
abstract: Macrophages constitute a major part of the cell response to wear particles produced at articulating and nonarticulating interfaces of joint replacements. This foreign body reaction can result in periprosthetic osteolysis and implant loosening. We demonstrate that ultra-high molecular weight polyethylene (UHMWPE) particles induce systemic trafficking of macrophages by noninvasive in vivo imaging and immunohistochemistry. The distal femora of nude mice were injected with 60 mg/mL UHMWPE suspension or saline alone. Reporter RAW264.7 macrophages that stably expressed the bioluminescent reporter gene and the fluorescence reporter gene were injected intravenously. Bioluminescence imaging was performed using an in vivo imaging system immediately after macrophage injection and at 2-day intervals. Compared with the nonoperated contralateral femora, at day 4, 6, and 8, the bioluminescent signal of femora containing UHMWPE suspension increased 1.30 +/- 0.09-, 2.36 +/- 0.92-, and 10.32 +/- 7.61-fold, respectively. The values at same time points for saline-injected control group were 1.08 +/- 0.07-, 1.14 +/- 0.27-, and 1.14 +/- 0.35-fold, respectively. The relative bioluminescence of the UHMWPE group was higher at all postinjection days and significantly greater than the saline group at day 8 (p < 0.05). Histological analysis confirmed the presence of reporter macrophages within the medullary canal of mice with implanted UHMWPE particles. The presence of UHMWPE particles induced enhanced bone remodeling activity. Clinically relevant UHMWPE particles stimulated the systemic recruitment of macrophages during an early time course using the murine femoral implant model. Interference with systemic macrophage trafficking may potentially mitigate UHMWPE particle-induced periprosthetic osteolysis.
authors.affiliation: Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Pei-Gen
authors.initials: PG
authors.lastname: Ren
authors.forename: Zhinong
authors.initials: Z
authors.lastname: Huang
authors.forename: Ting
authors.initials: T
authors.lastname: Ma
authors.forename: Sandip
authors.initials: S
authors.lastname: Biswal
authors.forename: Robert L
authors.initials: RL
authors.lastname: Smith
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
mesh_terms: D000818:Animals; D002460:Cell Line; D005549:Foreign-Body Reaction; D021621:Imaging, Three-Dimensional / Q000379:methods*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010316:Particle Size; D011095:Polyethylenes / Q000378:metabolism*; D011475:Prosthesis Failure
chemical_list: D011095:Polyethylenes; C111601:ultra-high molecular weight polyethylene