Mast cells and eosinophils: the “hallmark” of asthma (original) (raw)
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Mast cells are associated with exacerbations and eosinophilia in children with severe asthma
European Respiratory Journal, 2016
The role of mast cells in the pathogenesis of childhood asthma is poorly understood. We aimed to estimate the implication of airway mucosal mast cells in severe asthma and their relationship with clinical, functional, inflammatory and remodelling parameters.Bronchial biopsies were performed in 36 children (5–18 years) with severe asthma: 24 had frequent severe exacerbations and/or daily symptoms in the previous year (symptomatic group), and 12 had few symptoms and a persistent obstructive pattern (paucisymptomatic group). Nine children without asthma were included as control subjects. We assessed mast cells in the submucosa and airway smooth muscle using c-kit antibodies and in the entire biopsy area using Giemsa.The number of submucosal mast cells was higher in the symptomatic group than in the paucisymptomatic group (p=0.02). The number of submucosal mast cells correlated with the number of severe exacerbations (p=0.02, r=0.37). There were positive correlations between the number ...
The role of the mast cell in the pathophysiology of asthma
Journal of Allergy and Clinical Immunology, 2006
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 Ca 21 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. (J Allergy Clin
Key role for mast cells in nonatopic asthma
Journal of Allergy and Clinical Immunology, 2002
The mechanisms involved in non-atopic asthma are poorly defined. In particular, the importance of mast cells in the development of non-atopic asthma is not clear. In the mouse, pulmonary hypersensitivity reactions induced by skin sensitization with the low molecular weight compound dinitrofluorobenzene (DNFB) followed by an intra-airway application of the hapten have been featured as a model for non-atopic asthma. In the present study, we employed this model to examine the role of mast cells in the pathogenesis of non-atopic asthma. Firstly, the effect of DNFB sensitization and intra-airway challenge with dinitrobenzene sulphonic acid (DNS) on mast cell activation was monitored during the early phase of the response in BALB/c mice. Secondly, mast cell-deficient W/W v , Sl/Sl d mice and their respective normal (+/+) littermate mice and mast cell-reconstituted W/W v mice (BMMC→ W/W v ) were used. Early phase mast cell activation was found, which was maximal 30 min after DNS challenge in DNFB-sensitized BALB/c, +/+ mice, but not in mast cell-deficient mice. An acute bronchoconstriction and increase in vascular permeability accompanied the early phase mast cell activation. BALB/c, +/+ and BMMC→ W/W v mice sensitized with DNFB and DNS-challenged exhibited tracheal hyperreactivity 24 and 48 h after the challenge when compared to vehicle-treated mice. Mucosal exudation and infiltration of neutrophils in bronchoalveolar lavage fluid associated the late phase response.
Asthma is a chronic inflammatory disease of the lung and its pathophysiology is initiated by mast cell activation in response to the antigen binding to IgE receptor as well as by TH2 cell activation. Mast cells are well established effector cells in asthma where they exacerbate the inflammatory response, playing a key role in early phase, degranulating and increasing histamine. Human mast cells possess high affinity IgE receptors and are ubiquitous but predominantly localized in mucosal and connective tissue and are distributed along blood vessels. There are two types of mast cells: connective tissue mast cells (TC) and mucosal mast cells (T mast cells). TC mast cells contain more heparin, whereas T mast cells contain more chondroitin sulfate. In asthma, mast cell activation can trigger degranulation, releasing secretory granule complex and preformed mediators, such as histamine and proteases, along with the synthesis of leukotrines and prostaglandins, and induction of cytokines and chemokines. Leukotrine inhibitors and omalizumab, which inhibits IgE, both relieve the asthma exacerbation when administered to humans and permit to reduce the use of other drugs. The release of cytokines by mast cells, such as TNF-alpha, IL-1, IL-6 and IL-33, participate in the pathogenesis of asthma. Stress worsens asthma, and this effect is also mediated by mast cell activation through the release of cytokines. Administration of IL-33 in experimental animals provokes pathological effects in the mucosal tissues and augments antibody IgE and IgA in blood vessels. Here, we report the impact of mast cell biology in asthma pathogenesis.
Regulation of the inflammatory response in asthma by mast cell products
Immunology and Cell Biology, 2001
In airways, mast cells lie adjacent to nerves, blood vessels and lymphatics, which highlights their pivotal importance in regulating allergic inflammatory processes. In asthma, mast cells are predominantly activated by IgE receptor cross linking. In response to activation, preformed mediators that are stored bound to proteoglycans, for example, TNF-α, IL-4, IL-13, histamine, tryptase and chymase, are released. New synthesis of arachidonic acid metabolites (leukotriene C4 (LTC4), leukotriene B4 (LTB4) and prostaglandin D2 (PGD2)) and further cytokines is stimulated. Mediators from degranulating mast cells are critical to the pathology of the asthmatic lung. Mast cell proteases stimulate tissue remodelling, neuropeptide inactivation and enhanced mucus secretion. Histamine stimulates smooth muscle cell contraction, vasodilatation and increased venular permeability and further mucus secretion. Histamine induces IL-16 production by CD8 + cells and airway epithelial cells; IL-16 is an important early chemotactic factor for CD4 + lymphocytes. LTC4, LTB4 and PGD2 affect venular permeability and can regulate the activation of immune cells. The best characterized mast cell cytokine in asthmatic inflammation is TNF-α, which induces adhesion molecules on endothelial cells and subsequent transmigration of inflammatory leucocytes. IL-13 is critical to development of allergic asthma, although its mode of action is less clear.
The eosinophil and airway remodelling in asthma
The Clinical Respiratory Journal, 2010
Objectives: Eosinophils are common findings cells in allergic asthma as is sub-base membrane thickening of the airways. The objective of this review was to summarise some recent findings linking the activities of eosinophils to airways remodelling. Data Source and Study Selection: The study used a review of current literature with emphasis on our own recent findings. Results: Eosinophils are found at increased numbers in asthma and more so in allergic as compared with non-allergic asthma. A link has been found in several clinical studies on allergic asthmatics, but not in studies on non-allergic asthma, between the presence of eosinophils and signs of airways remodelling. The eosinophil contains and secretes several pro-fibrogenic molecules such as eosinophil cationic protein (ECP) and transforming growth factor b (TGF-b). Genetic studies on subjects developing liver fibrosis as a consequence of Schistosoma mansoni infection show close relationships to ECP genotypes. Conclusion: Several clinical and experimental studies indicate that eosinophils contribute to airways remodelling not only through their secretion of cationic proteins such as ECP and cytokines such as TGF-b1, but also through interactions with mast cells and epithelial cells. Please cite this paper as: Venge P. The eosinophil and airway remodelling in asthma.