Wound repair is a complex series of events that begins immediately after wounding, and can continue for a number of months to years. Various physiological and mechanical factors may impair the healing response, resulting in a chronic wound, characterised by a sustained inflammatory response. One of the main cells involved in both the inflammatory phase and proliferation phase of wound healing is the macrophage. There are thought to be different activation states which allow the macrophage to be involved in the two different phases of wound healing, namely the classically activated macrophage and the alternatively activated macrophage. Changes in the number of classically activated/alternatively activated macrophages in the wound is likely to have an effect on wound healing. Therefore a more thorough understanding of macrophage activation states during wound healing would broaden the understanding of the role of this cell in this process. The overall aim of this project was to investigate whether diabetic bone marrow progenitor cells or macrophages respond to activation stimuli differently in comparison to wild type cells. The hypothesis of this thesis is that diabetic macrophages will not respond to appropriate stimuli and thus alternative and classical macrophages will not behave 'appropriately', resulting in impaired healing. The results of this thesis indicate that impaired wound healing in the diabetic environment may be due to both the diabetic wound environment itself and intrinsic differences in diabetic macrophages. This work indicates that signals from the wound environment activates and influences macrophages, as these cells do not express activation markers until they enter the wound environment. However, the culture system devised in this study indicates that even before activation with signals they would receive in the wound environment, diabetic cells are more pro-inflammatory and have impaired migration. In addition, these macrophages respond differently to activation supporting the hypothesis that the macrophages are intrinsically different and that diabetic cells do not behave 'appropriately' which could contribute to impaired wound healing.
|Date of Award||1 Aug 2011|
- The University of Manchester
|Supervisor||Richard Grencis (Supervisor) & Kimberly Mace (Supervisor)|
- Classically Activated Macrophages, Alternatively Activated Macrophages, Wound Healing