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dc.contributor.authorRosbottom, Anneen
dc.date.accessioned2018-05-22T12:47:37Z
dc.date.available2018-05-22T12:47:37Z
dc.date.issued2002en
dc.identifier.urihttp://hdl.handle.net/1842/30701
dc.description.abstracten
dc.description.abstractMucosal mast cells (MMC) play a major role in allergic disease of the gut and in the immune response to gastrointestinal nematodes where, in the mouse, their precursors are recruited into the jejunum and migrate intraepithelially. There, they can be identified as the mature phenotype by their expression of the MMC-specific chymase, mouse mast cell protease-1 (mMCP-1).en
dc.description.abstractMigration of other immune cells is regulated by adhesion to extracellular matrix (ECM) proteins via expression of adhesion molecules such as integrins, and by interactions with chemotactic molecules such as chemokines. Previous work with other mast cell phenotypes suggests mast cells to be no exception to this regulatory system, therefore the aim of this project was to investigate the role of integrins and chemokines in mast cell migration.en
dc.description.abstractInitial experiments analysed, using RT-PCR, expression of potential mast cell chemoattractants from intestinal epithelium following infection of mice with the nematode parasite, Nippostrongylus brasiliensis. Chemokines MlP-la, RANTES, fractalkine and TECK, and cytokines SCF and TGF-Pi were constitutively expressed from intestinal epithelium; and MCP-1 expression was detected only on days 7 and 14 post-infection, coinciding with intraepithelial migration of mast cells. Cultured MMC and the CMT-93 intestinal epithelial cell line expressed some of these molecules, suggesting epithelial cells or intraepithelial MMC as potential sources of mast cell chemoattractants. Furthermore, expression of mRNA for chemokine receptors including CCR1, CCR2, CCR5, CX3CR1 and CXCR4 was detected in cultured MMC, possibly enabling migration towards chemokines expressed from intestinal epithelium.en
dc.description.abstractAdhesion of cultured MMC to ECM proteins was regulated by TGF-Pi, which also regulates the mucosal phenotype, as shown by expression of mMCP-1. MMC cultured with TGF-Pi adhered to laminin-1 via expression ofthe integrin a7pl, as demonstrated by RT-PCR, flow cytometry and use of neutralising antibodies. MMC cultured in the absence of TGF-Pi adhered to fibronectin and vitronectin but not laminin-1, and did not express a7pi. Expression of a7pi integrin has not previously been shown in a haemopoeitic cell and, as epithelial basement membranes are rich in laminin, this integrin may aid migration and retention of MMC intraepithelially.en
dc.description.abstractIn conclusion, this work suggests expression of integrins and chemokine receptors by MMC or their precursors, and of chemokines and cytokines by intestinal epithelium as possible mechanisms regulating intraepithelial migration of MMC.en
dc.publisherThe University of Edinburghen
dc.relation.ispartofAnnexe Thesis Digitisation Project 2018 Block 19en
dc.relation.isreferencedbyAlready catalogueden
dc.titleThe role of integrins and chemokines in the regulation of mucosal mast cell migration in the mouseen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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