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It is commonly accepted that macrophages predominantly drive the inflammatory response to wear debris particles. Among various surface receptors that activate the macrophages to phagocytize particles, it is believed that the Toll\u2010like receptor 4 (TLR4) and the scavenger macrophage receptor with collagenous structure (MARCO) play key roles in recognition of wear debris particles. However, a strong body of evidence indicates an age\u2010dependent diminished function of human TLRs. Thus, we hypothesized that the MARCO receptor may be more engaged than TLRs in the phagocytosis of wear debris particles which in turn up\u2010regulate production of pro\u2010inflammatory cytokines from aged macrophages. We demonstrated that peritoneal macrophages isolated from aged mice show elevated expression of MARCO receptor compared to that from young mice. In contrast the expression of TLR4 was significantly decreased on the surface of aged macrophages. Furthermore, using anti\u2010MARCO and anti\u2010TLR4 neutralizing mAbs, we demonstrated the age\u2010dependent pathogenic role of MARCO, but not TLR4, receptor in promoting poly\u2010methyl methacrylate (PMMA) bone cement particles phagocytosis by macrophages leading to the release of pro\u2010inflammatory cytokines migration inhibitory factor and tumour necrosis factor in vitro. These data also suggest that the approach to neutralize MARCO may lead to the development of therapeutic regimen for the prevention of particle\u2010induced osteolysis in aged patients.<\/jats:p>","DOI":"10.1111\/jcmm.14494","type":"journal-article","created":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T13:48:06Z","timestamp":1561124886000},"page":"5827-5831","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Age\u2010dependent effect between MARCO and TLR4 on PMMA particle phagocytosis by macrophages"],"prefix":"10.1111","volume":"23","author":[{"given":"Chiaki","family":"Yamada","sequence":"first","affiliation":[{"name":"College of Dental Medicine Nova Southeastern University Fort Lauderdale Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Beron\u2010Pelusso","sequence":"additional","affiliation":[{"name":"College of Dental Medicine Nova Southeastern University Fort Lauderdale Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neira","family":"Algazzaz","sequence":"additional","affiliation":[{"name":"Halmos College of Natural Science and Oceanography Nova Southeastern University Fort Lauderdale Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Heidari","sequence":"additional","affiliation":[{"name":"College of Dental Medicine Nova Southeastern University Fort Lauderdale Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diogo","family":"Luz","sequence":"additional","affiliation":[{"name":"College of Dental Medicine Nova Southeastern University Fort Lauderdale Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutasem","family":"Rawas\u2010Qalaji","sequence":"additional","affiliation":[{"name":"College of Pharmacy Nova Southeastern University Fort Lauderdale 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