TY - JOUR T1 - Mast cell regulation of airway smooth muscle function in asthma JF - European Respiratory Journal JO - Eur Respir J SP - 827 LP - 830 DO - 10.1183/09031936.00017707 VL - 29 IS - 5 AU - P. Bradding Y1 - 2007/05/01 UR - http://erj.ersjournals.com/content/29/5/827.abstract N2 - Asthma is a common disease affecting ≤10% of the adult Western population 1, 2. It is characterised by the presence of variable and potentially reversible airflow obstruction, which occurs as the result of bronchoconstriction, airway mucus plugging and airway oedema. Pathologically there is evidence of airway inflammation and remodelling 3–7. The mucosal inflammatory infiltrate commonly comprises activated T-cells, eosinophils and mast cells, while the accompanying structural changes include subepithelial collagen deposition, goblet cell- and mucous gland-hyperplasia, airway smooth muscle (ASM) hypertrophy and ASM hyperplasia. An important physiological feature of asthma is the presence of bronchial hyperresponsiveness (BHR) 8. This means there is an exaggerated bronchoconstrictor response of the ASM to direct and indirect stimuli such as histamine and exercise, respectively. While BHR is aggravated in the presence of classic allergic eosinophilic airway inflammation, it persists once this inflammation is controlled and is not present in patients with eosinophilic bronchitis 8, 9. This suggests that there is either a fundamental abnormality of ASM behaviour in asthmatic subjects or that there are interacting factors that have not been previously recognised. In support of the former, several phenotypic differences are evident in ASM cells cultured from the airways of asthmatic subjects. For example, when compared with normal ASM cells, cultured asthmatic ASM cells proliferate faster due to an altered pattern of matrix protein deposition 10, 11, secrete greater amounts of connective tissue-derived growth factor in response to transforming growth factor-β stimulation 12, and secrete markedly increased amounts of the chemokine CXCL10 in response to activation by cytokines 13. There is decreased expression of prostaglandin (PG)E2 by the asthmatic ASM 14, and proliferation of asthmatic ASM is not inhibited by corticosteroids due to impaired expression of the transcription factor CCAAT/enhancer … ER -