Characterisation of gastrointestinal microparticles

• Main Author: Thoree, Cheetranjan Vinay
• Published: King's College London (University of London) 2008
• Subjects: 612.3
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.555927

Intestinal Peyer's patches, through their specialized M cell-rich epithelium, can act as a portal of entry for bacteria, viruses, macromolecules and particles. Particles can be further classified as exogenous particles such as those derived from the diet in the form of food additives or endogenous particles which result from calcium and phosphate precipitation in the mid-distal intestinal lumen. Although exogenous dietary particles have been found to accumulate in "pigment cells" at the base of the human Peyer's patch, little is known about calcium phosphate particles. This thesis aimed (i) to investigate and compare the micro-anatomical site of exogenous and endogenous particles within the Peyer's patch, and (ii) to analyse the phenotype of cells involved in their uptake. Following an Introduction chapter (Chapter 1) and Methods chapter (Chapter 2), the focus of chapter 3 was to look for the presence of both calcium phosphate and exogenous particles in human intestinal Peyer's patches using the Von Kossa staining method and dark field microscopy, respectively. The elemental makeup of the endogenous particles was investigated by X-Ray Microanalysis (XRMA). This study revealed a sub-epithelial Peyer's patch dome-associated population of Von Kossapositive particle cells, the majority of which appeared to be calcium-rich, and more especially calcium- and phosphorus- rich. Exogenous particles associated with the usual basal pigment cells could similarly be found in the sub-epithelial dome cells and suggested that the exogenous particles made their way through the patch via intermediary cells. Following work concentrated on the phenotyping of cells responsible for the uptake of exogenous and endogenous particles (Chapters 4 and 5, respectively). Pigment cells of the Peyer's patch base were found to be macrophages, chiefly of a mature phenotype, and appeared metabolically and immunologically of low activation status. In contrast, calcium phosphate particles were found mainly in dendritic cells of the sub epithelial dome region of the Peyer's patch. The cell phenotype (CDIlc+, CDl lb+) was consistent with immune tolerance-inducing dendritic cells reported in the literature - the specific mechanism being induction of regulatory T cells. I have speculated on how the uptake of endogenous particles may influence such process.