- Professor Sampson's research over 38 years explored the roles of eicosanoids and related lipid mediators in inflammatory diseases to support the development of novel therapies and optimise the use of existing drugs. A number of studies characterised the cellular expression of enzymes of the leukotriene (5-lipoxygenase) and prostanoid (cyclooxygenase) pathways in human tissues in health and disease. These studies include immunohistochemical analyses of biopsies from patients with allergic asthma, aspirin-intolerant asthma, viral-induced wheezing, allergic rhinitis, urticaria and eczema. Distinct patterns of enzyme expression were related to disease severity and to responsiveness to triggers including allergens and aspirin. Measurements of lipids in bronchoalveolar lavage fluid, blood, urine and sputum have supplemented this approach, and a grant from the AAIR Charity helped to develop quantitative PCR assays for key enzymes and receptors. Professor Sampson's group was the first to identify abnormal expression of leukotriene C4 synthase (LTC4S) in the upper and lower airways as a key immunopathological characteristic underlying of Aspirin-Excerbated Respiratory Disease (AERD), a severe asthma syndrome associated with high mortality and acute sensitivity to NSAID ingestion.
- Barrett’s oesophagus is a premalignant condition associated with acid reflux which carries a high risk of progression to oesophageal adenocarcinoma. Previous studies have suggested an involvement of prostanoids in this progression, but in studies with Dr Praful Patel (Gastroenterology, SGH) and DM students funded by the Wessex Cancer Trust (Drs J Shutt, P Boger, J Neale) we showed relationships between 5-LO expression, leukotriene synthesis and disease status along the Barrett’s – adenocarcinoma spectrum. Laser microdissection is being applied to further localise these inflammatory changes.
- The group has a long history of interest in studying the immunological and genetic factors that regulate lipid mediator production and release in inflammatory cells isolated from the lungs and circulation of healthy donors and patients with airway disease. The capacity of cytokines to regulate the 5-LO pathway was studied in blood eosinophils and neutrophils and in lung epithelial cells and fibroblasts. We also explored the role of BLT2 receptors in T-lymphocyte proliferation and apoptosis (with Dr C Pickard and Prof E Healy). The isolation of cells from resected human lung tissue (with Dr Jane Warner) enabled new approaches relevant to lung disease, including a macrophage model of AERD and co-supervision of a new BBSRC/CASE studentship with GSK to examine angiotensin receptor pharmacology on human lung fibroblasts.
- In a cross-divisional collaboration with Dr Chris Torrens (HDH), we explored the potential of anti-inflammatory lipids including resolvins, lipoxins and protectins to relax human small bronchi and pulmonary vessels, or to reverse contractions induced by contractile lipids and other agonists, possibly at shared receptors. The work was funded by an integrated 4-year PhD studentship from the Gerald Kerkut Trust (Sampson, Warner, Torrens).
Dr A Sampson: 'Grant to support project evaluation of 5 lipoxygenase expression, intracellular localisation and quantification of mRNA levels in Barrett's metaplasia, dysplasia and adenocarinoma.'
Sponsor: Wessex Cancer Trust
Sponsor: Merck & Co Inc
Development and validation of quantitative pcr assays for lipid mediator pathways in human cells and tissues.
Sponsor: Aair Charity