by Joanne Van der Velden, Donna Barker, Garry Barcham, Emmanuel Koumoundouros, Kenneth Snibson

Increased 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.

MC 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 (MC_T and MC_TC respectively) was assessed by morphometric analysis of airway sections immunohistochemically stained with antibodies against MC tryptase and chymase.MC_T and MC_TC density was increased in small bronchi following 24 weeks of HDM challenges compared with controls (P<0.05). The MC_TC/MC_T ratio was significantly increased in HDM challenged sheep compared to controls (P<0.05). MC_T and MC_TC density was inversely correlated with allergen-induced increases in peripheral airway resistance after 24 weeks of allergen exposure (P<0.05). MC_T density was also negatively correlated with airway responsiveness after 24 challenges (P<0.01).

MC_T and MC_TC 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.