Rationale-IL-9 is a pleiotropic cytokine that has multiple effects on structural as well as numerous hematopoietic cells, which are central to the pathogenesis of asthma.Objectives-The contribution of IL-9 to asthma pathogenesis has thus far been unclear, due to conflicting reports in the literature. These earlier studies focused on the role of IL-9 in acute inflammatory models; here we have investigated the effects of IL-9 blockade during chronic allergic inflammation.Methods-Mice were exposed to either prolonged ovalbumin or house dust mite allergen challenge to induce chronic inflammation and airway remodeling.
Background: Lung mast cells are stereotypically divided into connective tissue (MC TC ) and mucosal (MC T ) mast cells. This study tests the hypothesis that each of these subtypes can be divided further into site-specific populations created by the microenvironment within each anatomical lung compartment. Methods: Surgical resections and bronchial and transbronchial biopsies from non-smoking individuals were obtained to study mast cells under non-inflamed conditions. Morphometric and molecular characteristics of mast cell populations were investigated in multiple lung structures by immunohistochemistry and electron microscopy. Results: MC T and MC TC coexisted in all compartments, with MC T being the prevailing type in bronchi, bronchioles and the alveolar parenchyma and MC TC being more abundant in pulmonary vessels and the pleura. Each of the MC TC and MC T phenotypes could be further differentiated into site-specific populations. MC TC were significantly larger in pulmonary vessels than in small airway walls, while the reverse was observed for MC T . Within each MC TC and MC T population there were also distinct sitespecific expression patterns of the IgE receptor, interleukin-9 receptor, renin, histidine decarboxylase, vascular endothelial growth factor, fibroblast growth factor, 5-lipoxygenase and leukotriene C4 synthase (eg, bronchial MC T consistently expressed more histidine decarboxylase than alveolar MC T ). Renin content was high in vascular MC TC but markedly lower in MC TC in other compartments. For both MC TC and MC T , the IgE receptor was highly expressed in conducting airways but virtually absent in alveolar parenchyma.Conclusions: These findings demonstrate novel sitespecific subpopulations of lung MC TC and MC T at baseline conditions. This observation may have important implications in the future exploration of mast cells in a number of pulmonary diseases.
Our data suggest that patients with atopic uncontrolled asthma have an increased parenchymal infiltration of MC(T) and MC(TC) populations with increased expression of FcεRI and surface-bound IgE compared with atopic and nonatopic controls.
As COPD progresses to its severe stages, the mast cell populations in the lung undergo changes in density, distribution, and molecular expression. In COPD lungs, these novel histopathological features were found to be correlated to lung function and they may thus have clinical consequences.
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