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Features of chronic asthma include airway hyperresponsiveness, inflammatory infiltrates, and structural changes in the airways, termed remodeling. The contribution of eosinophils, cells associated with asthma and allergy, remains to be established. We show that in mice with a total ablation of the eosinophil lineage, increases in airway hyperresponsiveness(More)
Airway inflammation and remodeling are important pathophysiologic features of chronic asthma. Previously, we have developed a mouse model of prolonged allergen challenge which exhibits many characteristics of chronic asthma such as goblet cell hyperplasia and subepithelial collagen deposition, in association with an increase in lung expression of the(More)
BACKGROUND Inflammatory infiltrates, airway hyper-responsiveness, goblet cell hyperplasia and subepithelial thickening are characteristic of chronic asthma. Current animal models of allergen-induced airway inflammation generally concentrate on the acute inflammation following allergen exposure and fail to mimic all of these features. OBJECTIVE The aim of(More)
Neutrophil entry into the lung tissues is a key step in host defense to bacterial and yeast infections, but if uncontrolled can lead to severe tissue damage. Here, we demonstrate for the first time that sialic acid binding Ig-like lectin E (siglec-E) functions to selectively regulate early neutrophil recruitment into the lung. In a model of acute lung(More)
BACKGROUND Airway inflammation and remodelling are important pathophysiologic features of chronic asthma. Although current steroid use demonstrates anti-inflammatory activity, there are limited effects on the structural changes in the lung tissue. OBJECTIVE We have used a mouse model of prolonged allergen challenge that exhibits many of the salient(More)
T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) is a surface molecule that is preferentially expressed on activated Th1 cells in comparison to Th2 cells. Blockade of Tim-3 has been shown to enhance Th1-driven pathology in vivo, suggesting that blockade of Tim-3 may improve the development of Th2-associated responses such as allergy. To(More)
Interleukin (IL)-9 is a pleiotropic cytokine secreted by T helper (Th)2 cells and has been proposed as a candidate gene for asthma and allergy. We have used mice genetically deficient in IL-9 to determine the role of this cytokine in the pathophysiologic features of the allergic pulmonary response-airway hyperreactivity (AHR) and eosinophilia. We have(More)
Treatment of patients with allergic asthma using low doses of peptides containing T cell epitopes from Fel d 1, the major cat allergen, reduces allergic sensitization and improves surrogate markers of disease. Here, we demonstrate a key immunological mechanism, linked epitope suppression, associated with this therapeutic effect. Treatment with selected(More)
Matrix metalloproteinases (MMPs) are a large family of endopeptidases that proteolytically degrade extracellular matrix. Many different cells produce MMP-9, and levels have been shown to be up-regulated in patients with allergic asthma. The aim of this study was to investigate the in vivo role of MMP-9 during allergen-induced airway inflammation. Acute(More)
Sialic-acid-binding immunoglobulin-like lectins (Siglecs) are members of the Ig superfamily that bind sialic acids in different linkages in a wide variety of glycoconjugates. These membrane receptors are expressed in a highly specific manner, predominantly within the haematopoietic system. The CD33-related Siglecs represent a distinct subgroup that is(More)