Abstract
BackgroundIncreased mast cell (MC) density and changes in their distribution in airway tissues is thought to contribute significantly to the pathophysiology of asthma. However, the time sequence for these changes and how they impact small airway function in asthma is not fully understood. The aim of the current study was to characterise temporal changes in airway MC density and correlate these changes with functional airway responses in sheep chronically challenged with house dust mite (HDM) allergen.Methodology/Principal FindingsMC density was examined on lung tissue from four spatially separate lung segments of allergic sheep which received weekly challenges with HDM allergen for 0, 8, 16 or 24 weeks. Lung tissue was collected from each segment 7 days following the final challenge. The density of tryptase-positive and chymase-positive MCs (MCT and MCTC respectively) was assessed by morphometric analysis of airway sections immunohistochemically stained with antibodies against MC tryptase and chymase.MCT and MCTC density was increased in small bronchi following 24 weeks of HDM challenges compared with controls (P<0.05). The MCTC/MCT ratio was significantly increased in HDM challenged sheep compared to controls (P<0.05). MCT and MCTC density was inversely correlated with allergen-induced increases in peripheral airway resistance after 24 weeks of allergen exposure (P<0.05). MCT density was also negatively correlated with airway responsiveness after 24 challenges (P<0.01).ConclusionsMCT and MCTC density in the small airways correlates with better lung function in this sheep model of chronic asthma. Whether this finding indicates that under some conditions mast cells have protective activities in asthma, or that other explanations are to be considered requires further investigation.
Highlights
Asthma is a chronic inflammatory disease of the airways, which is characterised by airway inflammation, reversible airflow limitation and hyperresponsive airways
MCT and MCTC density in the small airways correlates with better lung function in this sheep model of chronic asthma
Tryptase released by mast cell (MC) has been shown to induce airway inflammation and airway hyperresponsiveness (AHR) [1,2,3], while MC chymase promotes the recruitment of eosinophils and neutrophils to airway tissues [4]
Summary
Asthma is a chronic inflammatory disease of the airways, which is characterised by airway inflammation, reversible airflow limitation and hyperresponsive airways. Mast cells (MCs) are important mediator-secretor cells in allergic reactions and are thought to play a major role in the pathophysiology of asthma. Human MCs can be divided into two major groups based on their protease content. There are those that express tryptase but not chymase (MCT) and those that express tryptase and chymase (MCTC). These two MC phenotypes are known to differ in their tissue distribution and functional characteristics in healthy lungs, their relative contribution to the asthmatic phenotype is not fully understood. Increased mast cell (MC) density and changes in their distribution in airway tissues is thought to contribute significantly to the pathophysiology of asthma. The aim of the current study was to characterise temporal changes in airway MC density and correlate these changes with functional airway responses in sheep chronically challenged with house dust mite (HDM) allergen
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