Drug inhibition of the macrophage response to metal wear particles in vitro

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dc.contributor.authorHaynes, D.
dc.contributor.authorRogers, S.
dc.contributor.authorHowie, D.
dc.contributor.authorPearcy, M.
dc.contributor.authorVernon-Roberts, B.
dc.date.issued1996
dc.description.abstractThe wear particles of cobalt chrome alloy and titanium alloy have been implicated as a cause of aseptic loosening of prostheses. It is thought that their ability to induce either cell death or the release of mediators that induce bone resorption contributes to this loosening. This study was designed to test the hypothesis that these adverse biologic effects are due to wear particle corrosion at low pH after they have been phagocytosed by macrophages. Cobalt chrome alloy and titanium alloy particles of similar size and concentration to those found in the tissues surrounding failed prostheses were added to cultured rodent peritoneal macrophages. Treatment of macrophages with drugs that prevent a drop in pH within phagosomes significantly reduced the toxicity of phagocytosed cobalt chrome alloy particles. The same drugs also reduced the levels of prostaglandin E2 and interleukin-6 release induced by phagocytosed titanium alloy particles. When both types of particles were incubated at a low pH, similar to that encountered by phagocytosed particles, soluble products were released that induced the same effects as the particles themselves. These results show that enhanced corrosion of wear particles by phagocytic cells may contribute significantly to the adverse biologic effects of wear particles and identify drug therapies that may be investigated further.
dc.description.statementofresponsibilityDavid R. Haynes, Susan D. Rogers, Donald W. Howie, Mark J. Pearcy, and Barrie Vernon-Roberts
dc.identifier.citationClinical Orthopaedics and Related Research, 1996; 323(323):316-326
dc.identifier.doi10.1097/00003086-199602000-00045
dc.identifier.issn0009-921X
dc.identifier.issn1528-1132
dc.identifier.orcidHowie, D. [0000-0003-1702-3279]
dc.identifier.urihttp://hdl.handle.net/2440/6686
dc.language.isoen
dc.publisherLIPPINCOTT-RAVEN PUBL
dc.rights© 1996 Lippincott-Raven Publishers
dc.source.urihttps://doi.org/10.1097/00003086-199602000-00045
dc.subjectCells, Cultured
dc.subjectMacrophages
dc.subjectAnimals
dc.subjectRats
dc.subjectAmmonium Chloride
dc.subjectChromium Compounds
dc.subjectTitanium
dc.subjectMacrolides
dc.subjectPiroxicam
dc.subjectCytochalasin B
dc.subjectChloroquine
dc.subjectDinoprostone
dc.subjectInterleukin-6
dc.subjectAnti-Bacterial Agents
dc.subjectPhagocytosis
dc.subjectCorrosion
dc.subjectHydrogen-Ion Concentration
dc.titleDrug inhibition of the macrophage response to metal wear particles in vitro
dc.typeJournal article
pubs.publication-statusPublished

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