Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.700888
Title: Structural and functional role of CADM1 on mast cell-neuron cross-talk
Author: Magadmi, Rania
ISNI:       0000 0004 5989 3149
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2016
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Abstract:
Neuroimmune interactions are important in the pathophysiology of many chronic inflammatory diseases, particularly those associated with alterations in sensory processing and pain (Grace et al., 2014). Much of our understanding of these interactions comes from studies on mast cell- sensory neuron interactions in diseases such as irritable bowel syndrome (IBS) (Barbara et al., 2004). Mast cells and neurons are connected to each other both functionally and structurally. Cell adhesion molecule 1 (CADM1) has been identified as an adhesion molecule between mast cells and sensory neurons (Ito et al., 2008). However, it remains to be unclear if CADM1 is essential in mast cell-neuron functional cross-talk. The aim of this study is to investigate the role of CADM1- mediated adhesion between mast cell and neuron on IgE- mediated mast cell signalling and pro-inflammatory mediator secretion. Using the in vitro co-culture system of mouse bone marrow mast cells (BMMC) with sensory neurons isolated from dorsal root ganglions (DRG), expression and cellular distribution of CADM1 was determined. The adhesion between BMMC and sensory neurons was quantified using a fluorescent assay. Application of a CADM1 blocking peptide or knockdown CADM1 in BMMCs were found to significantly decrease both the BMMC attachment to sensory neurites, as well as, the enhancement of IgE-mediated BMMC degranulation in the presence of neurons. Furthermore, CADM1 Knockdown attenuates the enhancement of IL-6 release from BMMC in co-culture. Importantly, this study also showed that the CADM1-dependent enhancement of IgEmediated mast cell response is specific for neurons. It is suggested that neurons may mediate mast cell enhancement through action potential (AP)-independent neuropeptide release. In conclusion, my data have been revealed for first time the direct role of CADM1 in functional mast cell-sensory neuron cross-talk. Elucidating the precise mechanisms of CADM1 in IgE signaling is imperative for understanding many disease processes. The results of this study would contribute to the available knowledge about role of CADM1 in neuroimmune interactions and hold promise as a therapeutic target in various diseases such as IBS.
Supervisor: Seward, Elizabeth ; Furley, Andrew ; Damanhouri, Zoheir Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.700888  DOI: Not available
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