Pro-inflammatory chemokine CCL2 (MCP-1) promotes healing in diabetic wounds by restoring the macrophage response

Stephen Wood, Vijayakumar Jayaraman, Erica J. Huelsmann, Brian Bonish, Derick Burgad, Gayathri Sivaramakrishnan, Shanshan Qin, Luisa A. DiPietro, Andrew Zloza, Chunxiang Zhang, Sasha H. Shafikhani

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Prior studies suggest that the impaired healing seen in diabetic wounds derives from a state of persistent hyperinflammation characterized by harmful increases in inflammatory leukocytes including macrophages. However, such studies have focused on wounds at later time points (day 10 or older), and very little attention has been given to the dynamics of macrophage responses in diabetic wounds early after injury. Given the importance of macrophages for the process of healing, we studied the dynamics of macrophage response during early and late phases of healing in diabetic wounds. Here, we report that early after injury, the diabetic wound exhibits a significant delay in macrophage infiltration. The delay in the macrophage response in diabetic wounds results from reduced Chemokine (C-C motif) ligand 2 (CCL2) expression. Importantly, one-time treatment with chemoattractant CCL2 significantly stimulated healing in diabetic wounds by restoring the macrophage response. Our data demonstrate that, rather than a hyper-inflammatory state; the early diabetic wound exhibits a paradoxical and damaging decrease in essential macrophage response. Our studies suggest that the restoration of the proper kinetics of macrophage response may be able to jumpstart subsequent healing stages. CCL2 chemokine-based therapy may be an attractive strategy to promote healing in diabetic wounds.

Original languageEnglish (US)
Article numbere91574
JournalPloS one
Issue number3
StatePublished - Mar 11 2014
Externally publishedYes

ASJC Scopus subject areas

  • General


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