title: The macrophage inflammatory proteins MIP1α (CCL3) and MIP2α (CXCL2) in implant-associated osteomyelitis: linking inflammation to bone degradation.
abstract: Bacterial infections of bones remain a serious complication of endoprosthetic surgery. These infections are difficult to treat, because many bacterial species form biofilms on implants, which are relatively resistant towards antibiotics. Bacterial biofilms elicit a progressive local inflammatory response, resulting in tissue damage and bone degradation. In the majority of patients, replacement of the prosthesis is required. To address the question of how the local inflammatory response is linked to bone degradation, tissue samples were taken during surgery and gene expression of the macrophage inflammatory proteins MIP1α (CCL3) and MIP2α (CXCL2) was assessed by quantitative RT-PCR. MIPs were expressed predominantly at osteolytic sites, in close correlation with CD14 which was used as marker for monocytes/macrophages. Colocalisation of MIPs with monocytic cells could be confirmed by histology. In vitro experiments revealed that, aside from monocytic cells, also osteoblasts were capable of MIP production when stimulated with bacteria; moreover, CCL3 induced the differentiation of monocytes to osteoclasts. In conclusion, the multifunctional chemokines CCL3 and CXCL2 are produced locally in response to bacterial infection of bones. In addition to their well described chemokine activity, these cytokines can induce generation of bone resorbing osteoclasts, thus providing a link between bacterial infection and osteolysis.
authors.affiliation: Department of Orthopaedics and Trauma Surgery, University Hospital Heidelberg, Schlierbacher Landstraße 200a, 69118 Heidelberg, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Dapunt
authors.affiliation: Department of Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Maurer
authors.affiliation: Department of Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Giese
authors.affiliation: Department of Pathology, Heidelberg University, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany.
authors.forename: Matthias Martin
authors.initials: MM
authors.lastname: Gaida
authors.affiliation: Department of Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany.
authors.forename: Gertrud Maria
authors.initials: GM
authors.lastname: Hänsch
mesh_terms: D001862:Bone Resorption / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism*; D054426:Chemokine CXCL2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010019:Osteomyelitis / Q000276:immunology* / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000276:immunology; D013212:Staphylococcus epidermidis / Q000276:immunology; D013682:Teichoic Acids / Q000494:pharmacology
chemical_list: D054405:Chemokine CCL3; D054426:Chemokine CXCL2; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C009900:lipoteichoic acid