Limits...
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.

Show MeSH

Related in: MedlinePlus

Airway sections stained with antibodies against mast cell tryptase and chymase.(a) Tryptase-positive mast cells and (b) chymase-positive mast cells. The house dust mite (HDM) treated segment received 24 weekly challenges and the control segment was untreated. Negative control shows omission of the primary antibody. Arrows indicate positive cells.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3351402&req=5

pone-0037161-g002: Airway sections stained with antibodies against mast cell tryptase and chymase.(a) Tryptase-positive mast cells and (b) chymase-positive mast cells. The house dust mite (HDM) treated segment received 24 weekly challenges and the control segment was untreated. Negative control shows omission of the primary antibody. Arrows indicate positive cells.

Mentions: Results show that at least 16 weekly HDM challenges are required to increase the density of mast cells in the airway wall. MCT density in the airway wall of bronchi was significantly increased in HDM challenged segments that received 16 and 24 challenges compared to the corresponding segments in the control group (86±21 vs. 43±8, P<0.05 and 71±11 vs. 36±8 cells/mm2 respectively, P<0.05; Fig. 1). The mast cells were predominantly located in the outer walls of small bronchi as illustrated in Figure 2. There was no difference in MCT density in segments from HDM-challenged sheep that received 8 challenges compared to control sheep (Fig. 1). A correlation analysis revealed that MCT density in bronchi was significantly positively correlated to the duration in weeks of HDM challenges (rs = 0.510, P<0.01; data not shown).


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 sections stained with antibodies against mast cell tryptase and chymase.(a) Tryptase-positive mast cells and (b) chymase-positive mast cells. The house dust mite (HDM) treated segment received 24 weekly challenges and the control segment was untreated. Negative control shows omission of the primary antibody. Arrows indicate positive cells.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0037161-g002: Airway sections stained with antibodies against mast cell tryptase and chymase.(a) Tryptase-positive mast cells and (b) chymase-positive mast cells. The house dust mite (HDM) treated segment received 24 weekly challenges and the control segment was untreated. Negative control shows omission of the primary antibody. Arrows indicate positive cells.
Mentions: Results show that at least 16 weekly HDM challenges are required to increase the density of mast cells in the airway wall. MCT density in the airway wall of bronchi was significantly increased in HDM challenged segments that received 16 and 24 challenges compared to the corresponding segments in the control group (86±21 vs. 43±8, P<0.05 and 71±11 vs. 36±8 cells/mm2 respectively, P<0.05; Fig. 1). The mast cells were predominantly located in the outer walls of small bronchi as illustrated in Figure 2. There was no difference in MCT density in segments from HDM-challenged sheep that received 8 challenges compared to control sheep (Fig. 1). A correlation analysis revealed that MCT density in bronchi was significantly positively correlated to the duration in weeks of HDM challenges (rs = 0.510, P<0.01; data not shown).

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