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Investigation of pigmentation and immune-related cell surface molecules in cultured normal and vitiligo melanocytes.

Hedley, Susan Jennifer (1999) Investigation of pigmentation and immune-related cell surface molecules in cultured normal and vitiligo melanocytes. PhD thesis, University of Sheffield.

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Vitiligo is an acquired idiopathic hypomelanotic disorder which has an unknown aetiology and ultimately affects melanocytes, primarily of the skin. Many patients with vitiligo suffer from psychological distress and therefore it is important to determine why melanocytes are destroyed. The aim of this study was to learn more about the basic cellular physiology of normal and vitiligo melanocytes. Morphology, proliferation and pigmentation in normal melanocytes were highly influenced by media additives, bovine pituitary extract (BPE), cholera toxin (CT), foetal calf serum (FCS) and phorbol 12-myristate 13 acetate (PMA). In the absence of these factors, extracellular matrix (ECM) proteins increased survival, proliferation and pigmentation of normal melanocytes, while ultraviolet irradiation (UVR) increased dendricity and pigmentation in the presence of these factors. Normal and vitiligo melanocytes were morphologically very similar and long-term cultured vitiligo melanocytes had proliferation which was not significantly different to that of normal melanocytes. Constitutive and cytokine-stimulated expression of intercellular adhesion molecule-1 (ICAM-1), major histocompatibility complex (MHC) class I and II were not different between normal and vitiligo melanocytes in vitro. The latter suggested that vitiligo melanocytes do not have an inherent defect in regulation of these adhesion molecules which could lead to their premature interaction with the immune system. a-melanocyte stimulating hormone (a-MSH) has a controversial pigmentary role in man. In normal melanocytes, only under a limited number of media conditions did melanocytes exhibit increased melanogenesis to a-MSH. However a-MSH was found to be particularly effective at opposing the actions of TNF-a-stimulated ICAM-1 expression in melanocytes. This finding supported an immunomodulatory role for a-MSH in normal melanocytes. Finally a surgical treatment using cultured epithelial autograis (CEA) was used to treat 3 patients with symmetrical (generalised) vitiligo, with mixed results. One patient showed good repigmentation, while the response was less promising in the other-two patients.

Item Type: Thesis (PhD)
Keywords: Medicine
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Medicine (Sheffield)
Identification Number/EthosID: uk.bl.ethos.301850
Depositing User: EThOS Import Sheffield
Date Deposited: 03 Jun 2013 13:22
Last Modified: 08 Aug 2013 08:52
URI: http://etheses.whiterose.ac.uk/id/eprint/3483

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