Bacterial infections of bones remain a serious complication of endoprosthetic surgery. These infections are difficult to treat,\r\nbecause many bacterial species form biofilms on implants, which are relatively resistant towards antibiotics. Bacterial biofilms\r\nelicit a progressive local inflammatory response, resulting in tissue damage and bone degradation. In the majority of patients,\r\nreplacement of the prosthesis is required. To address the question of how the local inflammatory response is linked to bone\r\ndegradation, tissue samples were taken during surgery and gene expression of the macrophage inflammatory proteins MIP1a\r\n(CCL3) and MIP2?? (CXCL2) was assessed by quantitative RT-PCR. MIPs were expressed predominantly at osteolytic sites, in close\r\ncorrelation with CD14 which was used as marker for monocytes/macrophages. Colocalisation of MIPs with monocytic cells could\r\nbe confirmed by histology. In vitro experiments revealed that, aside from monocytic cells, also osteoblasts were capable of MIP\r\nproduction when stimulated with bacteria; moreover, CCL3 induced the differentiation of monocytes to osteoclasts. In conclusion,\r\nthe multifunctional chemokines CCL3 and CXCL2 are produced locally in response to bacterial infection of bones. In addition to\r\ntheir well described chemokine activity, these cytokines can induce generation of bone resorbing osteoclasts, thus providing a link\r\nbetween bacterial infection and osteolysis.
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