title: The response of macrophages to titanium particles is determined by macrophage polarization.
abstract: Aseptic loosening of total joint replacements is driven by the reaction of macrophages to foreign body particles released from the implant. It was hypothesized that the macrophages' response to these particles is dependent, in addition to particle characteristics and contaminating biomolecules, on the state of macrophage polarization as determined by the local cytokine microenvironment. To test this hypothesis we differentiated M1 and M2 macrophages from human peripheral blood monocytes and compared their responses to titanium particles using genome-wide microarray analysis and a multiplex cytokine assay. In comparison to non-activated M0 macrophages, the overall chemotactic and inflammatory responses to titanium particles were greatly enhanced in M1 macrophages and effectively suppressed in M2 macrophages. In addition, the genome-wide approach revealed several novel, potentially osteolytic, particle-induced mediators, and signaling pathway analysis suggested the involvement of toll-like and nod-like receptor signaling in particle recognition. It is concluded that the magnitude of foreign body reaction caused by titanium particles is dependent on the state of macrophage polarization. Thus, by limiting the action of M1 polarizing factors, e.g. bacterial biofilm formation, in peri-implant tissues and promoting M2 macrophage polarization by biomaterial solutions or pharmacologically, it might be possible to restrict wear-particle-induced inflammation and osteolysis.
authors.affiliation: Institute of Biomedicine, Anatomy, University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014 University of Helsinki, Finland; Department of Medicine, Institute of Clinical Medicine, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 8, P.O. Box 20, 00029 HUS, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Pajarinen
authors.forename: Vesa-Petteri
authors.initials: VP
authors.lastname: Kouri
authors.forename: Eemeli
authors.initials: E
authors.lastname: Jämsen
authors.forename: Tian-Fang
authors.initials: TF
authors.lastname: Li
authors.forename: Jami
authors.initials: J
authors.lastname: Mandelin
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D000328:Adult; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D016764:Cell Polarity / Q000187:drug effects* / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D063990:Gene Ontology; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis; D052638:Particulate Matter / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects / Q000235:genetics; D040081:Protein Array Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014025:Titanium / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D055815:Young Adult
chemical_list: D016207:Cytokines; D052638:Particulate Matter; D014025:Titanium
keywords: Foreign body response; Joint replacement; Macrophage; Titanium; Wear debris