Roles of Mast Cells in Asthma

Asthma Free Forever

Asthma Free Forever By Jerry Ericson

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Allergic asthma is a chronic disease of the respiratory tract (41). It is characterized by relapsing-remitting episodes of reversible airway obstruction. Clinical symptoms include shortness of breath, wheezing, chest discomfort, and coughing, which can lead to respiratory failure. Eosinophilia, lung inflammation, elevated serum IgE, mucus hypersecretion, and hyperreactive airways are typical. Like immediate hypersensitive responses, allergens elicit the initial symptoms, and mast cell mediators promote early bronchial constriction, airway edema, and mucus plugging as well as recruitment of eosinophils. Lymphocytes and eosinophils are recruited within 24 h and contribute to the disordered airway physiology and early remodeling. Because mast cell-stabi-

Site of initial allergen entry mast cell allergens^ < *

mast cell allergens^ < *

immature DC

Lymph node

Target organ: Skin/Lung/GI

lL-4-driven IgE isotype switching y lL-4-driven IgE isotype switching y

Mast Cell Recruitment Skin

Degranu iati on/ Cytokine synthesis mediator release and secretion

antigen-specitic Th2

antigen-specitic Th2

Mast cell + antigen-

Degranu iati on/ Cytokine synthesis mediator release and secretion

Fig. 1. Mast cells act at multiple sites to modulate allergic inflammation. (A) Mast cells may be directly activated by allergen and through the release of mediators and interaction with dendritic cell (DC) CD40 alter DC maturation and migration. (B) In the lymph node, cytokines such as IL-4, expressed by mast cells or histamine, directly influence the differentiation of naive allergen-specific T-helper cells upon antigen (allergen) presentation by DCs and promote the differentiation of Th2 cells capable of IL-4 and IL-13 secretion. (C) Activated Th2 cells, in conjunction with allergen, can stimulate allergen-specific B cells and promote B cell isotype switching to IgE. Mast cells may also have a direct role in inducing IgE production via IL-4 and interaction with CD40 on B cells. (D) Within the target organ (e.g., lung, skin, or gastrointestinal tract), allergen-specific IgE binds to the high-affinity FceRI receptor expressed on resident mast cells. Crosslinking of the FceRI/IgE complexes on mast cells by subsequent exposure to allergen leads to mast cell degranulation and release of proinflammatory mediators.

lizing drugs have little value in treating chronic asthma, it has been assumed that mast cells do not contribute to later events in the pathophysiology of this disease.

However, recent data from human studies strongly suggest that mast cells are intimately involved. Mast cells are prevalent within the bronchial smooth muscle, and their density correlates with indices of bronchial hyperrespon-siveness. Tryptase, a mast cell specific mediator, induces airway smooth muscle hyperplasia and also affects lung epithelial cells by promoting fibrosis. Long-term effects likely include the irreversible alterations in airway anatomy and decline in lung function with time. Animal models of asthma are limited in their ability to recapitulate chronic asthma and, thus, an in vivo demonstration of the effects of mast cells on chronic asthma has not been established.

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Coping with Asthma

Coping with Asthma

If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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