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It was hypothesized that foreign body wear debris induces it to participate in handling of implant\u2010derived particles in human synovial membrane\u2010like tissue around aseptically loosening total hip replacement implants. A DNA microarray study showed that MARCO was upregulated in human monocytes by polymethyl methacrylate particles in cell culture. MARCO mRNA and protein were strongly expressed in numerous CD68 positive macrophages and foreign body giant cells in interface membrane lining and stroma around cemented implants, but was only present in a few cells in synovial membrane from osteoarthritis patients. A 65\u2010kDa MARCO\u2010reactive band was only found in interface tissue extracts. This is the first work to show upregulation of MARCO mRNA by foreign bodies <jats:italic>in vitro<\/jats:italic>. This is paralleled <jats:italic>in vivo<\/jats:italic> as MARCO mRNA and protein were over\u2010expressed in chronic foreign body synovitis. As scavenger receptor MARCO apparently participates in handling of wear particles, which due to their nondegradable, irritating nature initiate\/perpetuate foreign body inflammation, and peri\u2010implant osteolysis. \u00a9 2009 Wiley Periodicals, Inc. 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