Circulating blood monocytes traffic to and participate in the periprosthetic tissue inflammation.
OBJECTIVE
To examine the trafficking of human circulating blood monocytes and their influence on the inflammation of periprosthetic tissues using a novel mouse-human chimera model.


METHODS
Periprosthetic tissue and bone chips from patients with aseptic prosthetic loosening were implanted into the muscles of immune-deficient SCID mice depleted of host macrophages by periodic intraperitoneal injection of anti-asialo GM1 rabbit sera (ASGM1). Autologous patient peripheral blood monocytes (PBMCs) were labeled with PKH2 fluorescent dye and injected intraperitoneally into the implanted animals. Mice were sacrificed 14 days after PBMC transfusion for molecular and histological analyses.


RESULTS
Patient periprosthetic tissues were well tolerated in SCID mice and preserved a high level of viability. Cell trafficking studies revealed the accumulation of fluorescent PBMC within the xenografts, with total cell counts in the xenografts significantly increased following the systemic PBMC infusion. PBMC infusion also promoted the expression of IL-1, IL-6, TNFalpha, and RANK within the periprosthetic tissue.


CONCLUSIONS
Systemic PBMC migrated to the implanted periprosthetic tissues and contributed to the local inflammation. The data provide evidence that circulating blood monocytes may play a role in pathologic process during aseptic loosening of total joint replacement.
Zhang
Kai
K
Shandong University School of Medicine, Jinan, China.
Jia
Tang-Hong
TH
McQueen
David
D
Gong
Wei-Ming
WM
Markel
David C
DC
Wooley
Paul H
PH
Yang
Shang-You
SY
D000818:Animals; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D007595:Joint Prosthesis; D051379:Mice; D016513:Mice, SCID; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D011475:Prosthesis Failure; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation; D014183:Transplantation, Heterologous / Q000276:immunology*
D005456:Fluorescent Dyes; D012333:RNA, Messenger