2006
DOI: 10.1172/jci25702
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Mast cells can promote the development of multiple features of chronic asthma in mice

Abstract: Bronchial asthma, the most prevalent cause of significant respiratory morbidity in the developed world, typically is a chronic disorder associated with long-term changes in the airways. We developed a mouse model of chronic asthma that results in markedly increased numbers of airway mast cells, enhanced airway responses to methacholine or antigen, chronic inflammation including infiltration with eosinophils and lymphocytes, airway epithelial goblet cell hyperplasia, enhanced expression of the mucin genes Muc5a… Show more

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Cited by 254 publications
(277 citation statements)
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“…First, mast cells amplify allergic asthma symptoms in a similar model of asthma (without alum adjuvant) (29). Second, mast cells are hyperplasic in the lungs of asthmatic mice, and the pre-existing mast cell hyperplasia of the lungs in Ship1 Ϫ/Ϫ -BMMC mice would likely predispose them to heightened allergic asthma pathology (30). Third, IL-6 and TNF, inflammatory cytokines associated with increased asthma pathology, are elevated in the serum of Ship1 Ϫ/Ϫ -BMMC mice (20,31).…”
Section: Discussionmentioning
confidence: 99%
“…First, mast cells amplify allergic asthma symptoms in a similar model of asthma (without alum adjuvant) (29). Second, mast cells are hyperplasic in the lungs of asthmatic mice, and the pre-existing mast cell hyperplasia of the lungs in Ship1 Ϫ/Ϫ -BMMC mice would likely predispose them to heightened allergic asthma pathology (30). Third, IL-6 and TNF, inflammatory cytokines associated with increased asthma pathology, are elevated in the serum of Ship1 Ϫ/Ϫ -BMMC mice (20,31).…”
Section: Discussionmentioning
confidence: 99%
“…Interestingly, the depletion of CD4ϩ cells in our study was greater than 95% effective, whereas levels of inflammation were ϳ50% of control mice. Thus, although CD4ϩ cells play a substantial role in chronic inflammation, CD4-independent mechanisms that support recruitment and maintenance of inflammatory cells are operable, which might include chemokine and cytokine release from mast cells, eosinophils, and airway epithelium (6,14,17,39). Most significantly, although it is recognized that CD4ϩ cells are required at an early stage to allow initiation of the airway remodeling process, our data strongly demonstrate that CD4ϩ cells are not collectively required after an initial acute lung inflammatory response for the structural features of remodeling to develop.…”
Section: Discussionmentioning
confidence: 99%
“…37,40,58 The DSS model of colitis is a nonallergic model in which eosinophilia is commonly noted, but there are no studies examining the role of mast cells in eosinophil accumulation in this setting. Our results demonstrate that, when colitis is induced, eosinophil accumulation to the submucosa of the cecum and midcolon occurs independently of mast cells (Figure 4).…”
Section: Discussionmentioning
confidence: 99%