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Mediators of Inflammation
Volume 2014, Article ID 728619, 10 pages
Research Article

The Macrophage Inflammatory Proteins MIP1 (CCL3) and MIP2 (CXCL2) in Implant-Associated Osteomyelitis: Linking Inflammation to Bone Degradation

1Department of Orthopaedics and Trauma Surgery, University Hospital Heidelberg, Schlierbacher Landstraße 200a, 69118 Heidelberg, Germany
2Department of Immunology, Heidelberg University, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany
3Department of Pathology, Heidelberg University, Im Neuenheimer Feld 224, 69120 Heidelberg, Germany

Received 16 January 2014; Accepted 18 February 2014; Published 25 March 2014

Academic Editor: Marc Pouliot

Copyright © 2014 Ulrike Dapunt et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.