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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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Relationship between mast cell density and peak early bronchoconstriction response.Correlation between the percentage increase in peripheral resistance (Rp) 30 minutes post-HDM challenge and (a) MCT (rs = −0.89, P<0.05) and (b) MCTC (rs = −0.82, P<0.05).
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pone-0037161-g004: Relationship between mast cell density and peak early bronchoconstriction response.Correlation between the percentage increase in peripheral resistance (Rp) 30 minutes post-HDM challenge and (a) MCT (rs = −0.89, P<0.05) and (b) MCTC (rs = −0.82, P<0.05).

Mentions: Next we tested whether increased mast cell density in the small airways was correlated to the lung function indices reported in our previous study. MCT density in bronchi after 24 weeks of challenges was significantly negatively correlated with the peak early-phase airway response (EAR); i.e. percent increase in Rp from baseline following a HDM challenge (rs = −0.96, P<0.05; Fig. 4a). There was no correlation between MC density and EAR at any of the other time-points (data not shown). MCTC density after 24 weeks of HDM challenges was also negatively correlated with early-phase responses (rs = −0.82, P<0.05; Fig. 4b).


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)

Relationship between mast cell density and peak early bronchoconstriction response.Correlation between the percentage increase in peripheral resistance (Rp) 30 minutes post-HDM challenge and (a) MCT (rs = −0.89, P<0.05) and (b) MCTC (rs = −0.82, P<0.05).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0037161-g004: Relationship between mast cell density and peak early bronchoconstriction response.Correlation between the percentage increase in peripheral resistance (Rp) 30 minutes post-HDM challenge and (a) MCT (rs = −0.89, P<0.05) and (b) MCTC (rs = −0.82, P<0.05).
Mentions: Next we tested whether increased mast cell density in the small airways was correlated to the lung function indices reported in our previous study. MCT density in bronchi after 24 weeks of challenges was significantly negatively correlated with the peak early-phase airway response (EAR); i.e. percent increase in Rp from baseline following a HDM challenge (rs = −0.96, P<0.05; Fig. 4a). There was no correlation between MC density and EAR at any of the other time-points (data not shown). MCTC density after 24 weeks of HDM challenges was also negatively correlated with early-phase responses (rs = −0.82, P<0.05; Fig. 4b).

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