title: Titanium uptake, induction of RANK-L expression, and enhanced proliferation of human T-lymphocytes.
abstract: There is increasing evidence that titanium ions are released from orthopedic implants by biocorrosion. The aim of this study was to investigate titanium uptake by human T-lymphocytes and its effects on phenotype and proliferation. Freshly isolated human nonadherent peripheral blood mononuclear cells (NA-PBMC), were exposed to TiCl4 [Ti(IV)]. Bioavailability and distribution of Ti(IV) in T-lymphocytes was determined by energy-filtered electron microscopy (EFTEM). The effects of Ti(IV) challenge on nonactivated and PHA-activated cells were assessed by flow cytometric analysis of surface markers, RANK-L production, and proliferation assays. EFTEM colocalized Ti(IV) with phosphorus in the nucleus, ribosomes, cytoplasmic membranes, and the surface membrane of T-lymphocytes. Ti(IV) increased significantly the expression of CD69, CCR4, and RANK-L in a concentration-dependent manner. Titanium enters T-lymphocytes through a currently unknown mechanism and binds to phosphorus-rich cell structures. Titanium influences phenotype and function of T-lymphocytes, resulting in activation of a CD69+ and CCR4+ T-lymphocyte population and secretion of RANK-L. These results strongly suggest the involvement of titanium ions challenged T-lymphocytes in the complex pathophysiological mechanisms of aseptic loosening of orthopedic implants.
authors.affiliation: School of Anatomy and Human Biology, University of Western Australia, 35 Stirling Highway, Crawley, Australia 6009. dcadosch@gmx.net
authors.forename: Dieter
authors.initials: D
authors.lastname: Cadosch
authors.forename: Michael
authors.initials: M
authors.lastname: Sutanto
authors.forename: Erwin
authors.initials: E
authors.lastname: Chan
authors.forename: Amir
authors.initials: A
authors.lastname: Mhawi
authors.forename: Oliver P
authors.initials: OP
authors.lastname: Gautschi
authors.forename: Brilliana
authors.initials: B
authors.lastname: von Katterfeld
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Simmen
authors.forename: Luis
authors.initials: L
authors.lastname: Filgueira
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001682:Biological Availability; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D008854:Microscopy, Electron / Q000379:methods; D010641:Phenotype; D010835:Phytohemagglutinins / Q000494:pharmacology; D053245:RANK Ligand / Q000032:analysis / Q000096:biosynthesis*; D054398:Receptors, CCR4 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism* / Q000502:physiology; D014018:Tissue Distribution; D014025:Titanium / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D003470:Culture Media; D037181:Lectins, C-Type; D010835:Phytohemagglutinins; D053245:RANK Ligand; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D014025:Titanium; D000099192:CD69 Antigens; C515354:CCR4 protein, human; C505688:TNFSF11 protein, human; C025096:titanium tetrachloride