Implant wear induced inflammation is mitigated in CX3CR1(-/-) mice.
Wear debris-induced monocyte recruitment plays a key role in the formation of chronic periprosthetic tissue inflammation associated with aseptic loosening. The purpose of this study was to investigate the role(s) of chemokine receptor CX3CR1 in ultra high molecular weight polyethylene (UHMWPE) particle-induced tissue inflammation using a murine air pouch model developed in CX3CR1 knockout (CX3CR1(-/-) ) mice. UHMWPE debris or saline were introduced into established air pouches on CX3CR1(-/-) and CX3CR1(+/+) mice. Pouch tissues were collected 7 days after UHMWPE inoculation. Results showed that UHMWPE stimulation induced strong pouch tissue inflammation in CX3CR1(+/+) mice, as manifested by inflammatory cellular infiltration (mainly macrophages), pouch tissue proliferation, and increased gene expression of IL-1ß and TNFα. UHMWPE-induced inflammation was significantly mitigated in CX3CR1(-/-) mice, as manifested by reduction of tissue inflammation (pouch thickness and cell density), inflammatory cytokine production (IL-1ß and TNFα) and macrophage accumulation. The observations support the hypothesis that the activation of the CX3CR1 chemokine pathway contributes to the severity of UHMWPE particle-induced tissue inflammation, and suggests that CX3CR1 signaling is involved in the recruitment of monocytes to the wear debris-containing inflammatory tissues. Blocking of CX3CR1 pathway may represent a viable therapeutic approach to the prevention and treatment of patients with aseptic loosening.
Department of Biomedical Engineering, Wayne State University, Detroit, Michigan; Department of Orthopaedic Surgery, Providence Hospital, Southfield, Michigan.
Weiping
W
Ren
Nancy
N
Jackson
Wei
W
Song
Tong
T
Shi
Jeffrey C
JC
Flynn
David C
DC
Markel
D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1 / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000096:biosynthesis; D008264:Macrophages / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D011095:Polyethylenes / Q000009:adverse effects*; D011475:Prosthesis Failure / Q000209:etiology*; D019707:Receptors, Chemokine / Q000172:deficiency* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; C471885:Cx3cr1 protein, mouse; D053583:Interleukin-1beta; D011095:Polyethylenes; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; C111601:ultra-high molecular weight polyethylene
CX3CL1; CX3CR1; animal model; cell trafficking; inflammation; wear debris