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Role of mast cells and basophils in different phenotypes of asthma

Madeleine Rådinger, Krefting Research Centre, University of Gothenburg, Sweden

Background
Mast cells and basophils play important roles as the primary effectors cells in anaphylaxis and allergic reactions, such as allergen induced asthma. Central to their role in asthma is their expression of the high affinity Fc receptor for IgE (FcεRI). Antigen-mediated FcεRI aggregation is the major activation for mast cells in vivo and leads to a coordinated activation of intracellular signaling pathways that result in degranulation of preformed mediators and synthesis and secretion of de novo synthesized lipid mediators, chemokines and cytokines. Thus, mast cell derived mediators, such as histamine, leukotrines (LTC4), prostaglandins and cytokines are well recognized to be responsible for the IgE-dependent reactions in acute asthma, anaphylactic reactions and allergic rhinitis.

Aim
The aim of this project is to determine whether specific mast cell-related disease states, such as in allergic asthma, are associated with abnormalities in signaling processes required for mast cell activation via FcεRI or KIT, the two key receptors expressed on mast cells. We hypothesize that mast cells from asthmatics subjects have a higher releasability in response to antigen, which further involves downstream signaling molecules. In some experiments, basophil activation will also be examined.

Methodology
Mast cells and basophils from asthmatics and non-asthmatic controls will be screened for differences in antigen-mediated releaseability, such as degranulation. If differences are found in antigen-mediated degranulation within asthmatic groups and in comparison to non-asthmatic controls, we will investigate the causative differences in signaling molecules/pathways in response to antigen/FcεRI and/or stem cell factor (SCF)/KIT -mediated activation.

Importance
Although mast cells, basophils and their secreted mediators have been implicated in the allergen induced asthma responses over the last decades, direct analysis of the signaling changes in the FcεRI and/or KIT pathways that may contribute to the enhanced releasability of “asthmatic mast cells”, has not yet been reported. A greater understanding about the molecular mechanisms leading to mast cell and basophil activation in allergic diseases such as asthma, might lead to development of new therapeutic targets.

Human Mast cells

Human Mast cells

Human mast cells cultured from peripheral blood in SCF and IL-6 stained with toluidine blue

Page Manager: Madeleine Ahrnens|Last update: 12/1/2009
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