The role of the mast cell in the pathophysiology of asthma - 20/08/11
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Leicester and Southampton, United Kingdom
Abstract |
There is compelling evidence that human mast cells contribute to the pathophysiology of asthma. Mast cells, but not T cells or eosinophils, localize within the bronchial smooth muscle bundles in patients with asthma but not in normal subjects or those with eosinophilic bronchitis, a factor likely to be important in determining the asthmatic phenotype. The mechanism of mast cell recruitment by asthmatic airway smooth muscle involves the CXCL10/CXCR3 axis, and several mast cell mediators have profound effects on airway smooth muscle function. The autacoids are established as potent bronchoconstrictors, whereas the proteases tryptase and chymase are being demonstrated to have a range of actions consistent with key roles in inflammation, tissue remodeling, and bronchial hyperresponsiveness. IL-4 and IL-13, known mast cell products, also induce bronchial hyperresponsiveness in the mouse independent of the inflammatory response and enhance the magnitude of agonist-induced intracellular Ca2+ responses in cultured human airway smooth muscle. There are therefore many pathways by which the close approximation of mast cells with airway smooth muscle cells might lead to disordered airway smooth muscle function. Mast cells also infiltrate the airway mucous glands in subjects with asthma, showing features of degranulation, and a positive correlation with the degree of mucus obstructing the airway lumen, suggesting that mast cells play an important role in regulating mucous gland secretion. The development of potent and specific inhibitors of mast cell secretion, which remain active when administered long-term to asthmatic airways, should offer a novel approach to the treatment of asthma.
Le texte complet de cet article est disponible en PDF.Key words : Mast cells, asthma, airway smooth muscle, bronchial mucous glands, chemokines, TNF-⍺
Abbreviations used : ASM, BHR, EB, HLMC, LT, PAR, PG, SCF, SHIP, TLR
Plan
Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. |
Vol 117 - N° 6
P. 1277-1284 - juin 2006 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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