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The role of the mast cell in the pathophysiology of asthma

The role of the mast cell in the pathophysiology of asthma
The role of the mast cell in the pathophysiology of asthma
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.
mast cells, asthma, airway smooth muscle, bronchial mucous glands, chemokines
0091-6749
1277-1284
Bradding, Peter
9cbfd3d1-1bf2-484f-849f-0bf4ffbacc19
Walls, Andrew F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Bradding, Peter
9cbfd3d1-1bf2-484f-849f-0bf4ffbacc19
Walls, Andrew F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc

Bradding, Peter, Walls, Andrew F. and Holgate, Stephen T. (2006) The role of the mast cell in the pathophysiology of asthma. Journal of Allergy and Clinical Immunology, 117 (6), 1277-1284. (doi:10.1016/j.jaci.2006.02.039).

Record type: Article

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.

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More information

Published date: June 2006
Keywords: mast cells, asthma, airway smooth muscle, bronchial mucous glands, chemokines

Identifiers

Local EPrints ID: 59272
URI: https://eprints.soton.ac.uk/id/eprint/59272
ISSN: 0091-6749
PURE UUID: d1eb0fda-fa51-4017-bf9a-cdd0c8fd5259

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Date deposited: 02 Sep 2008
Last modified: 13 Mar 2019 20:30

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