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Title: An investigation into intestinal uptake of microparticles and relevance to disease
Author: Mazumder, Ramendra Nath
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2002
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A model to study uptake of inert microparticles and recombinant bovine prions across human colon mucosa has been developed. Uptake of inert microparticles was examined by confocal and electron microscopic studies in cultured human colon mucosa. Also, the effect of lipopolysaccharide on the uptake of inert microparticles by inflamed colon mucosa was studied. Lipopolysaccharide had no effect on the morphology of human colon epithelium as examined by light and electron microscopy. In uptake studies with organ culture, the numbers of inert microparticles in inflamed intestinal mucosa were greater than in normal intestine. The numbers of microparticles were increased significantly in lipopolysaccharide-treated inflamed tissue. The Increased formation of macropinosomes indirectly in response to LPS may explain the observed increased uptake of inert microparticles in IBD. An image analysis technique was applied to quantify microparticle-laden macrophages and revealed a significant increase in microparticle-laden macrophages in Crohn’s disease. By X-ray microanalysis, inorganic microparticles were confirmed as compounds of titanium, silicon, aluminium and chromium. Detection of chromium in resected human intestine has not been reported before. Chromium has been reported as granulogenic in other tissues, but not in the intestine. This in vitro model was successfully applied to study uptake of recombinant bovine prions in human intestinal epithelial cells. This study has shown for the first time that human colonic cells can take up microparticles in vitro and that this uptake is enhanced in the presence of inflammation. It is further enhanced in the presence of LPS. Microparticles of aluminium, silicon, titanium and chromium may be found within the macrophages in inflamed intestinal mucosa from IBD patients. Chromium is granulogenic in certain tissues. Recombinant bovine prion protein can also be taken up by intestinal mucosa in vitro.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available