Burn injury to skin changes the chemical composition of the skin interstitium and induces a complex inflammatory response proportionate to the amount of skin damaged. This PhD aims to better characterise the chemical composition of skin following burn injury to develop deeper understanding of the pathological processes involved and how these contribute to the complexity of burn injury.
42 patients were recruited at a specialist burn centre. Samples of burn skin and uninjured control skin were analysed using metabolomic (i.e. desorption electrospray ionisation mass spectrometry), functional enzymatic staining (i.e. lactate dehydrogenase) and cellular (i.e. immunohistochemistry (IHC)) imaging.
Using DESI-MS distinct patterns of variation were demonstrated between burn and control skin, reaching statistical significance using supervised and unsupervised univariate and multivariate analyses. Network analysis demonstrated distinct patterns of variable correlation across the samples. Differentiating variables included phospholipid species, lysophospholipids, free fatty acids and small compounds with anti-oxidant properties all of which were increased in intensity in burn tissue. Whilst apparent differences were noted between burns of different ages, and of different mechanisms of injury, these did not reach statistical significance. Using functional and cellular imaging, patterns were identified that linked inflammatory cell infiltration, principally lymphocytes and macrophages, to metabolically active burn tissue. Further, there was a marked difference in the distribution in the tissue of compounds with antioxidative properties within burn skin as highlighted by a novel length regression analysis tool. These results indicate inflammatory cell mediated tissue responses, utilising phospholipase A2 activity pathways, and profound antioxidant activity are directly involved in burn tissue responses. Additionally, this thesis introduces a novel mechanistic understanding of how burn injury may have shaped human culture-gene co-evolution through the introduction of a uniquely human selective pressure – high temperature burn injury.