Receptor tyrosine kinase regulation of mast cell-airway smooth muscle beta2-adrenoceptor function in asthma. (360G-Wellcome-094058_Z_10_Z)
Beta2-adrenoceptor agonists form a cornerstone of asthma treatment by reversing and/or preventing bronchoconstriction. However, in some subjects beta2-adrenoceptor agonists are of poor efficacy, particularly during acute exacerbations, and regular use may lead to deterioration in asthma control. The mechanisms are poorly understood. Mast cell infiltration of the airway smooth muscle (ASM) in asthma is a characteristic feature of the asthmatic phenotype. Mast cells interact intimately with ASM th rough bi-directional cell-cell and mediator-dependent effects. Interestingly, human lung mast cell (HLMC) beta2-adrenoceptor responses are attenuated within minutes of exposure to stem cell factor due to beta2-adrenoceptor phosphorylation on Tyr350 and receptor internalisation. We hypothesise that mast cell-ASM cross-talk leads to beta2-adrenoceptor uncoupling in both cell types through receptor tyrosine kinase activity. If true, targeting these pathways may enhance beta2-agonist efficacy and sa fety in asthma. We will test this hypothesis by investigating: 1. The ability of HLMC and ASM-derived growth factors to phosphorylate and uncouple beta2-adrenoceptor agonist responses in these cells. 2. The ability of ASM in co-culture with HLMC to inhibit HLMC beta2-adrenoceptor agonist responses, and vice versa. 3. Expression of phosphorylated beta2-adrenoceptors in bronchial biopsies from subjects with asthma compared to healthy controls, and their correlation with clinical measurements .
Where is this data from?
This data was originally published by The Wellcome Trust. If you see something about your organisation or the funding it has received on this page that doesn't look right you can submit a grantee amendment request. You can hover over codes from standard codelists to see the user-friendly name provided by 360Giving.
Grant Details
Amount Awarded | 162905 |
Applicant Surname | Amrani |
Approval Committee | Physiological Sciences Funding Committee |
Award Date | 2011-03-15T00:00:00+00:00 |
Financial Year | 2010/11 |
Grant Programme: Title | Project Grant |
Internal ID | 094058/Z/10/Z |
Lead Applicant | Dr Yassine Amrani |
Other Applicant(s) | Prof Chris Brightling, Prof Peter Bradding |
Partnership Value | 162905 |
Planned Dates: End Date | 2014-12-31T00:00:00+00:00 |
Planned Dates: Start Date | 2011-07-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | East Midlands |