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Increased mast cell density and airway responses to allergic and non-allergic stimuli in a sheep model of chronic asthma.

Van der Velden J, Barker D, Barcham G, Koumoundouros E, Snibson K - PLoS ONE (2012)

Bottom Line: 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) density was also negatively correlated with airway responsiveness after 24 challenges (P<0.01).

View Article: PubMed Central - PubMed

Affiliation: Centre for Animal Biotechnology, Veterinary Science, University of Melbourne, Parkville, Australia.

ABSTRACT

Background: 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.

Methodology/principal findings: 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).

Conclusions: 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.

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Related in: MedlinePlus

Airway remodeling and eosinophils following chronic allergen challenge.(a) Airway smooth muscle (ASM) per mm basement membrane (BM) length (b) collagen area per mm BM and (c) eosinophils per mm2 airway wall, in untreated control sheep and sheep challenged with house dust mite (HDM) allergen weekly for 24 weeks. Line shows the mean, boxes show 25th and 75th percentile, whiskers represent 5th to 95th percentile. n = 7, *P<0.05, ***P<0.001 compared to controls.
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pone-0037161-g006: Airway remodeling and eosinophils following chronic allergen challenge.(a) Airway smooth muscle (ASM) per mm basement membrane (BM) length (b) collagen area per mm BM and (c) eosinophils per mm2 airway wall, in untreated control sheep and sheep challenged with house dust mite (HDM) allergen weekly for 24 weeks. Line shows the mean, boxes show 25th and 75th percentile, whiskers represent 5th to 95th percentile. n = 7, *P<0.05, ***P<0.001 compared to controls.

Mentions: There was no significant difference in the amount of ASM in the lung segment that received 24 weeks of HDM compared to the corresponding segment in controls (0.029±0.005 vs. 0.025±0.004 mm2/BM; Fig. 6a). However, there was a significant increase in the amount of collagen (0.17±0.02 vs. 0.11±0.02 mm2/BM, P<0.05 Fig. 6b). There was a trend for the increase in collagen to be associated with increasing MCTC density (rs = 0.71, P = 0.088). The amount of airway collagen also tended to be negatively associated with EAR (rs = −0.75, P = 0.066).


Increased mast cell density and airway responses to allergic and non-allergic stimuli in a sheep model of chronic asthma.

Van der Velden J, Barker D, Barcham G, Koumoundouros E, Snibson K - PLoS ONE (2012)

Airway remodeling and eosinophils following chronic allergen challenge.(a) Airway smooth muscle (ASM) per mm basement membrane (BM) length (b) collagen area per mm BM and (c) eosinophils per mm2 airway wall, in untreated control sheep and sheep challenged with house dust mite (HDM) allergen weekly for 24 weeks. Line shows the mean, boxes show 25th and 75th percentile, whiskers represent 5th to 95th percentile. n = 7, *P<0.05, ***P<0.001 compared to controls.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351402&req=5

pone-0037161-g006: Airway remodeling and eosinophils following chronic allergen challenge.(a) Airway smooth muscle (ASM) per mm basement membrane (BM) length (b) collagen area per mm BM and (c) eosinophils per mm2 airway wall, in untreated control sheep and sheep challenged with house dust mite (HDM) allergen weekly for 24 weeks. Line shows the mean, boxes show 25th and 75th percentile, whiskers represent 5th to 95th percentile. n = 7, *P<0.05, ***P<0.001 compared to controls.
Mentions: There was no significant difference in the amount of ASM in the lung segment that received 24 weeks of HDM compared to the corresponding segment in controls (0.029±0.005 vs. 0.025±0.004 mm2/BM; Fig. 6a). However, there was a significant increase in the amount of collagen (0.17±0.02 vs. 0.11±0.02 mm2/BM, P<0.05 Fig. 6b). There was a trend for the increase in collagen to be associated with increasing MCTC density (rs = 0.71, P = 0.088). The amount of airway collagen also tended to be negatively associated with EAR (rs = −0.75, P = 0.066).

Bottom Line: 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) density was also negatively correlated with airway responsiveness after 24 challenges (P<0.01).

View Article: PubMed Central - PubMed

Affiliation: Centre for Animal Biotechnology, Veterinary Science, University of Melbourne, Parkville, Australia.

ABSTRACT

Background: 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.

Methodology/principal findings: 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).

Conclusions: 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.

Show MeSH
Related in: MedlinePlus