期刊
MOLECULAR IMMUNOLOGY
卷 47, 期 2-3, 页码 175-184出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2009.09.023
关键词
UHMWPE; Aseptic osteolysis; Endosomal damage; Inflammation
资金
- NIAID NIH HHS [R56 AI072667, AI 48832, R56 AI072667-01, R01 AI048832] Funding Source: Medline
- NIA NIH HHS [R01 AG045223] Funding Source: Medline
- NINDS NIH HHS [T32 NS007098, T32 NS 07098] Funding Source: Medline
Ultra-high molecular weight polyethylene is widely used as a bearing surface in prosthetic arthroplasty. Over time the generation of implant-derived wear particles can initiate an inflammatory reaction characterized by periprosthetic inflammation and ultimately bone resorption at the prosthetic bone interface. Herein we present evidence that the different sized particles as well as the different length alkane polymers generated by implant wear leads to a two component inflammatory response. Polymeric alkane structures, with side chain oxidations, directly bind and activate the TLR-1/2 signaling pathway. Whereas micron- and nanometer-sized particulate debris are extensively phagocyted and induce enlargement, fusion and disruption of endosomal compartments. The resulting lysosomal damage and subsequent enzymatic leakage induces the NALP3 inflammasome activation as determined by cathepsins S and B cytosolic release, Caspase 1 activation and processing of pro-IL-1 beta, and pro-IL-18. These two processes synergistically results in the initiation of a strong inflammatory response with consequent cellular necrosis and extracellular matrix degradation. (C) 2009 Elsevier Ltd. All rights reserved.
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