{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:41:19Z","timestamp":1791304879482,"version":"4.3.1"},"reference-count":46,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T00:00:00Z","timestamp":1362096000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T00:00:00Z","timestamp":1362096000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cellular Immunology"],"published-print":{"date-parts":[[2013,3]]},"DOI":"10.1016\/j.cellimm.2013.04.003","type":"journal-article","created":{"date-parts":[[2013,4,23]],"date-time":"2013-04-23T21:00:52Z","timestamp":1366750852000},"page":"53-65","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":64,"title":["Toll-like receptor 4 signaling pathway mediates proinflammatory immune response to cobalt-alloy particles"],"prefix":"10.1016","volume":"282","author":[{"given":"Pushya A.","family":"Potnis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debargh K.","family":"Dutta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven C.","family":"Wood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cellimm.2013.04.003_b0005","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1243\/09544119JEIM112","article-title":"Wear particles from metal-on-metal total hip replacements: effects of implant design and implantation time","volume":"220","author":"Catelas","year":"2006","journal-title":"Proc. Inst. Mech. Eng. H"},{"key":"10.1016\/j.cellimm.2013.04.003_b0010","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1002\/jor.21458","article-title":"Calcineurin\/nuclear factor of activated T cells (NFAT) signaling in cobalt\u2013chromium\u2013molybdenum (CoCrMo) particles-induced tumor necrosis factor-alpha (TNFalpha) secretion in MLO-Y4 osteocytes","volume":"29","author":"Orhue","year":"2011","journal-title":"J. Orthop. Res."},{"key":"10.1016\/j.cellimm.2013.04.003_b0015","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mrgentox.2010.01.012","article-title":"The in vitro genotoxicity of orthopaedic ceramic (Al2O3) and metal (CoCr alloy) particles","volume":"697","author":"Tsaousi","year":"2010","journal-title":"Mutat. Res."},{"key":"10.1016\/j.cellimm.2013.04.003_b0020","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.biomaterials.2004.04.035","article-title":"The role of macrophages in osteolysis of total joint replacement","volume":"26","author":"Ingham","year":"2005","journal-title":"Biomaterials"},{"key":"10.1016\/j.cellimm.2013.04.003_b0025","first-page":"182","article-title":"Biologic effects of implant debris","volume":"67","author":"Hallab","year":"2009","journal-title":"Bull. NYU Hosp. Joint Dis."},{"key":"10.1016\/j.cellimm.2013.04.003_b0030","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1302\/0301-620X.91B6.21844","article-title":"Circulating levels of cobalt and chromium from metal-on-metal hip replacement are associated with CD8+ T-cell lymphopenia","volume":"91","author":"Hart","year":"2009","journal-title":"J. Bone Joint Surg. Br."},{"key":"10.1016\/j.cellimm.2013.04.003_b0035","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1302\/0301-620X.91B10.22308","article-title":"Blood metal ion concentrations after hip resurfacing arthroplasty: a comparative study of articular surface replacement and Birmingham hip resurfacing arthroplasties","volume":"91","author":"Langton","year":"2009","journal-title":"J. Bone Joint Surg. Br."},{"key":"10.1016\/j.cellimm.2013.04.003_b0040","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1016\/j.arth.2011.03.037","article-title":"Serum metal ion concentrations after unilateral vs bilateral large-head metal-on-metal primary total hip arthroplasty","volume":"26","author":"Pelt","year":"2011","journal-title":"J. Arthroplas."},{"key":"10.1016\/j.cellimm.2013.04.003_b0045","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1002\/1097-4636(20010905)56:3<427::AID-JBM1112>3.0.CO;2-E","article-title":"Differential lymphocyte reactivity to serum-derived metal-protein complexes produced from cobalt-based and titanium-based implant alloy degradation","volume":"56","author":"Hallab","year":"2001","journal-title":"J. Biomed. Mater. Res."},{"key":"10.1016\/j.cellimm.2013.04.003_b0050","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1002\/jbm.a.31467","article-title":"Human macrophage response to UHMWPE, TiAlV, CoCr, and alumina particles: analysis of multiple cytokines using protein arrays","volume":"84","author":"Kaufman","year":"2008","journal-title":"J. Biomed. Mater. Res. A"},{"key":"10.1016\/j.cellimm.2013.04.003_b0055","doi-asserted-by":"crossref","first-page":"526","DOI":"10.3109\/17453674.2010.519169","article-title":"Effects of metal-on-metal wear on the host immune system and infection in hip arthroplasty","volume":"81","author":"Hosman","year":"2010","journal-title":"Acta Orthop."},{"key":"10.1016\/j.cellimm.2013.04.003_b0060","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1098\/rsif.2008.0142","article-title":"The combined role of wear particles, macrophages and lymphocytes in the loosening of total joint prostheses","volume":"5","author":"Revell","year":"2008","journal-title":"J. R. Soc. Interface"},{"key":"10.1016\/j.cellimm.2013.04.003_b0065","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1243\/095441105X63291","article-title":"Biological effects of clinically relevant wear particles from metal-on-metal hip prostheses","volume":"220","author":"Brown","year":"2006","journal-title":"Proc. Inst. Mech. Eng. H"},{"key":"10.1016\/j.cellimm.2013.04.003_b0070","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1002\/jor.20826","article-title":"Soluble and particulate Co\u2013Cr\u2013Mo alloy implant metals activate the inflammasome danger signaling pathway in human macrophages: a novel mechanism for implant debris reactivity","volume":"27","author":"Caicedo","year":"2009","journal-title":"J. Orthop. Res."},{"key":"10.1016\/j.cellimm.2013.04.003_b0075","first-page":"1055","article-title":"The potential role of human osteoblasts for periprosthetic osteolysis following exposure to wear particles","volume":"28","author":"Lochner","year":"2011","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.cellimm.2013.04.003_b0080","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3109\/1547691X.2011.553845","article-title":"Effect of chromium and cobalt ions on primary human lymphocytes in vitro","volume":"8","author":"Akbar","year":"2011","journal-title":"J. Immunotoxicol."},{"key":"10.1016\/j.cellimm.2013.04.003_b0085","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/0142-9612(94)90170-8","article-title":"Cell damage in vitro following direct contact with fine particles of titanium, titanium alloy and cobalt-chrome-molybdenum alloy","volume":"15","author":"Evans","year":"1994","journal-title":"Biomaterials"},{"key":"10.1016\/j.cellimm.2013.04.003_b0090","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s11420-006-9003-6","article-title":"The central role of wear debris in periprosthetic osteolysis","volume":"2","author":"Purdue","year":"2006","journal-title":"HSS J."},{"key":"10.1016\/j.cellimm.2013.04.003_b0095","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1189\/jlb.1208763","article-title":"TLR4\/MyD88\/PI3K interactions regulate TLR4 signaling","volume":"85","author":"Laird","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"10.1016\/j.cellimm.2013.04.003_b0100","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1359\/jbmr.2001.16.11.2082","article-title":"Adherent endotoxin on orthopedic wear particles stimulates cytokine production and osteoclast differentiation","volume":"16","author":"Bi","year":"2001","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.cellimm.2013.04.003_b0105","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1002\/jbm.a.32474","article-title":"The roles of monocytic heat shock protein 60 and Toll-like receptors in the regional inflammation response to wear debris particles","volume":"92","author":"Hao","year":"2010","journal-title":"J. Biomed. Mater. Res. A"},{"key":"10.1016\/j.cellimm.2013.04.003_b0110","doi-asserted-by":"crossref","first-page":"32378","DOI":"10.1074\/jbc.M110.136895","article-title":"Bacterial pathogen-associated molecular patterns stimulate biological activity of orthopaedic wear particles by activating cognate Toll-like receptors","volume":"285","author":"Greenfield","year":"2010","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.cellimm.2013.04.003_b0115","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1124\/jpet.106.104265","article-title":"Polymyxin B-conjugated alpha 2-macroglobulin as an adjunctive therapy to sepsis: modes of action and impact on lethality","volume":"318","author":"Birkenmeier","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.cellimm.2013.04.003_b0120","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/sj.cdd.4401850","article-title":"TLR signaling","volume":"13","author":"Kawai","year":"2006","journal-title":"Cell Death Differ."},{"key":"10.1016\/j.cellimm.2013.04.003_b0125","doi-asserted-by":"crossref","first-page":"e1009","DOI":"10.3928\/01477447-20120621-12","article-title":"Metal-on-metal total hip arthroplasty: causes and high incidence of early failure","volume":"35","author":"Fabi","year":"2012","journal-title":"Orthopedics"},{"key":"10.1016\/j.cellimm.2013.04.003_b0130","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.molmed.2011.12.002","article-title":"Molecular and immune toxicity of CoCr nanoparticles in MoM hip arthroplasty","volume":"18","author":"Gill","year":"2012","journal-title":"Trends Mol. Med."},{"key":"10.1016\/j.cellimm.2013.04.003_b0135","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1002\/(SICI)1097-4636(19991215)47:4<543::AID-JBM11>3.0.CO;2-G","article-title":"Effects of metal ions on white blood cells of patients with failed total joint arthroplasties","volume":"47","author":"Savarino","year":"1999","journal-title":"J. Biomed. Mater. Res."},{"issue":"Suppl. 2","key":"10.1016\/j.cellimm.2013.04.003_b0140","doi-asserted-by":"crossref","first-page":"107","DOI":"10.2106\/JBJS.J.01721","article-title":"Cobalt and chromium levels in blood and urine following hip resurfacing arthroplasty with the Conserve Plus implant","volume":"93","author":"Kim","year":"2011","journal-title":"J. Bone Joint Surg. Am."},{"key":"10.1016\/j.cellimm.2013.04.003_b0145","doi-asserted-by":"crossref","first-page":"S206","DOI":"10.1097\/00003086-199608001-00018","article-title":"Metal versus polyethylene wear particles in total hip replacements. A review","author":"Doorn","year":"1996","journal-title":"Clin. Orthop. Relat. Res."},{"key":"10.1016\/j.cellimm.2013.04.003_b0150","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1002\/jbm.a.32627","article-title":"Soluble ions more than particulate cobalt-alloy implant debris induce monocyte costimulatory molecule expression and release of proinflammatory cytokines critical to metal-induced lymphocyte reactivity","volume":"93","author":"Caicedo","year":"2010","journal-title":"J. Biomed. Mater. Res. A"},{"key":"10.1016\/j.cellimm.2013.04.003_b0155","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.2106\/00004623-199608000-00014","article-title":"Characterization and comparison of wear debris from failed total hip implants of different types","volume":"78","author":"Hirakawa","year":"1996","journal-title":"J. Bone Joint Surg. Am."},{"key":"10.1016\/j.cellimm.2013.04.003_b0160","doi-asserted-by":"crossref","first-page":"653","DOI":"10.3109\/17453670903473016","article-title":"Necrotic and inflammatory changes in metal-on-metal resurfacing hip arthroplasties","volume":"80","author":"Mahendra","year":"2009","journal-title":"Acta Orthop."},{"key":"10.1016\/j.cellimm.2013.04.003_b0165","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.nano.2011.08.002","article-title":"Characterization of metal-wear nanoparticles in pseudotumor following metal-on-metal hip resurfacing","volume":"7","author":"Xia","year":"2011","journal-title":"Nanomedicine"},{"key":"10.1016\/j.cellimm.2013.04.003_b0170","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1007\/s11999-010-1372-y","article-title":"Histological features of pseudotumor-like tissues from metal-on-metal hips","volume":"468","author":"Campbell","year":"2010","journal-title":"Clin. Orthop. Relat. Res."},{"issue":"Suppl. 1","key":"10.1016\/j.cellimm.2013.04.003_b0175","doi-asserted-by":"crossref","first-page":"S42","DOI":"10.5435\/00124635-200800001-00010","article-title":"What are the local and systemic biologic reactions and mediators to wear debris, and what host factors determine or modulate the biologic response to wear particles?","volume":"16","author":"Tuan","year":"2008","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"10.1016\/j.cellimm.2013.04.003_b0180","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1002\/art.21238","article-title":"Innate immunity conferred by Toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation","volume":"52","author":"Liu-Bryan","year":"2005","journal-title":"Arthritis Rheum."},{"key":"10.1016\/j.cellimm.2013.04.003_b0185","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/ni.1919","article-title":"Crucial role for human Toll-like receptor 4 in the development of contact allergy to nickel","volume":"11","author":"Schmidt","year":"2010","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.cellimm.2013.04.003_b0190","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1177\/09680519030090010801","article-title":"Overexpression of CD14, TLR4, and MD-2 in HEK 293T cells does not prevent induction of in vitro endotoxin tolerance","volume":"9","author":"Medvedev","year":"2003","journal-title":"J. Endotoxin Res."},{"key":"10.1016\/j.cellimm.2013.04.003_b0195","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1189\/jlb.1009674","article-title":"Involvement of TLR2 and TLR4 in cell responses to Rickettsia akari","volume":"88","author":"Quevedo-Diaz","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"10.1016\/j.cellimm.2013.04.003_b0200","doi-asserted-by":"crossref","first-page":"10689","DOI":"10.1074\/jbc.274.16.10689","article-title":"Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction","volume":"274","author":"Chow","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.cellimm.2013.04.003_b0205","doi-asserted-by":"crossref","first-page":"455","DOI":"10.2106\/00004623-200004000-00001","article-title":"A potential concern in total joint arthroplasty: systemic dissemination of wear debris","volume":"82","author":"Clark","year":"2000","journal-title":"J. Bone Joint Surg. Am."},{"key":"10.1016\/j.cellimm.2013.04.003_b0210","doi-asserted-by":"crossref","first-page":"17615","DOI":"10.1073\/pnas.0906541106","article-title":"Endosomes: a legitimate platform for the signaling train","volume":"106","author":"Murphy","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.cellimm.2013.04.003_b0215","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1002\/jbm.a.10169","article-title":"Metal ions alter lipopolysaccharide-induced NF kappa B binding in monocytes","volume":"67","author":"Lewis","year":"2003","journal-title":"J. Biomed. Mater. Res. A"},{"key":"10.1016\/j.cellimm.2013.04.003_b0220","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/jbm.a.30383","article-title":"Au(III), Pd(II), Ni(II), and Hg(II) alter NF kappa B signaling in THP1 monocytic cells","volume":"74","author":"Lewis","year":"2005","journal-title":"J. Biomed. Mater. Res. A"},{"key":"10.1016\/j.cellimm.2013.04.003_b0225","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1046\/j.1365-2842.2002.00893.x","article-title":"Human peripheral blood monocytes versus THP-1 monocytes for in vitro biocompatibility testing of dental material components","volume":"29","author":"Heil","year":"2002","journal-title":"J. Oral. Rehabil."},{"key":"10.1016\/j.cellimm.2013.04.003_b0230","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1002\/jor.1100150107","article-title":"Human monocyte\/macrophage response to cobalt-chromium corrosion products and titanium particles in patients with total joint replacements","volume":"15","author":"Lee","year":"1997","journal-title":"J. Orthop. Res."}],"container-title":["Cellular Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0008874913000543?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0008874913000543?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T18:19:53Z","timestamp":1762107593000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0008874913000543"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["S0008874913000543"],"URL":"https:\/\/doi.org\/10.1016\/j.cellimm.2013.04.003","relation":{},"ISSN":["0008-8749"],"issn-type":[{"value":"0008-8749","type":"print"}],"subject":[],"published":{"date-parts":[[2013,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Toll-like receptor 4 signaling pathway mediates proinflammatory immune response to cobalt-alloy particles","name":"articletitle","label":"Article Title"},{"value":"Cellular Immunology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cellimm.2013.04.003","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}