Endocrine Abstracts (2012) 28 P206

Retention of Leukocytes in the Diabetic Wound Environment

Jayne Charnock, Enrique Gallego & Kimberly Mace

The Healing Foundation Centre, The University of Manchester, Manchester, United Kingdom.

Inadequate wound repair, observed in 15% of diabetics, leads to a chronic wound phenotype and is the leading cause of non-traumatic amputation in the developed world today. Injury induces recruitment of bone marrow-derived cells (BMDCs) to the wound in response to chemoattactant signals, which then contribute to the repair and regeneration process, initially through their role in the inflammatory response. Both granulocytes and monocytes are fundamental at this early stage, but aberrant recruitment and/or retention of these cells is believed to prolong the inflammatory response in diabetic wounds and fails to promote transition into the tissue regeneration phase, leading to chronic inflammation and impaired healing. The regulation of behavior of BMDC is, however, poorly understood. In this study we aim to further investigate the role of inflammatory mediators in normal versus chronic diabetic wounds using a mouse model where we hypothesize that the diabetic wound environment itself may impair recruitment, retention, or function of BMDC. We have characterised and isolated granulocyte and monocyte populations in BM of wild-type and Lepr-/- (diabetic) C57BL/6 mice. Recruitment kinetics of subsets of these cells (CCR2+ monocytes and CXCR2+ granulocytes) in response to chemoattractants, as well as the effects of specific inhibitor compounds, were investigated using in vitro migration studies. An in vivo wounding assay was developed in which wild-type and diabetic mouse BMD CXCR2+ granulocytes were injected into wounds of recipient wild-type or diabetic animals. Inflammatory cell retention in the diabetic environment is increased in comparison to the normal environment, irrespective of donor cell genotype. These findings suggest that the diabetic wound environment may result in dysfunctional inflammatory cell behaviour and could be the focus for the identification of therapeutic targets in the treatment of chronic wounds.

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.

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