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Association of mast cells with lung function in chronic obstructive pulmonary disease.

Gosman MM, Postma DS, Vonk JM, Rutgers B, Lodewijk M, Smith M, Luinge MA, Ten Hacken NH, Timens W - Respir. Res. (2008)

Bottom Line: In asthma, higher chymase positive mast cell (MC-C) numbers are associated with less airway obstruction.Numbers of MC-T and MC-C were determined in different regions of central and peripheral airways and percentage of degranulation was determined.In COPD, MC-T numbers in the airway wall and more specifically in the epithelium and subepithelial area of peripheral airways correlated positively with FEV1/VC (Spearman's rho (rs) 0.47, p = 0.05 and rs 0.48, p = 0.05, respectively); MC-C numbers in airway smooth muscle of peripheral airways correlated positively with FEV1% predicted (rs 0.57, p = 0.02).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pulmonology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands. margotgosman@hotmail.com

ABSTRACT

Background: In asthma, higher chymase positive mast cell (MC-C) numbers are associated with less airway obstruction. In COPD, the distribution of MC-C and tryptase positive mast cells (MC-T) in central and peripheral airways, and their relation with lung function, is unknown. We compared MC-T and MC-C distributions in COPD and controls without airflow limitation, and determined their relation with lung function.

Methods: Lung tissue sections from 19 COPD patients (median [interquartile range] FEV1% predicted 56 [23-75]) and 10 controls were stained for tryptase and chymase. Numbers of MC-T and MC-C were determined in different regions of central and peripheral airways and percentage of degranulation was determined.

Results: COPD patients had lower MC-T numbers in the subepithelial area of central airways than controls. In COPD, MC-T numbers in the airway wall and more specifically in the epithelium and subepithelial area of peripheral airways correlated positively with FEV1/VC (Spearman's rho (rs) 0.47, p = 0.05 and rs 0.48, p = 0.05, respectively); MC-C numbers in airway smooth muscle of peripheral airways correlated positively with FEV1% predicted (rs 0.57, p = 0.02). Both in COPD patients and controls the percentage of degranulated MC-T and MC-C mast cells was higher in peripheral than in central airways (all p < 0.05), but this was not different between the groups.

Conclusion: More MC-T and MC-C in peripheral airways correlate with better lung function in COPD patients. It is yet to determine whether this reflects a protective association of mast cells with COPD pathogenesis, or that other explanations are to be considered.

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1a. (left) Double immunostaining: tryptase positive mast cells (bright red) in a small airway in a tissue sample from a patient with moderate COPD (GOLD stage 2); bronchial and alveolar type 2 epithelial cells and smooth muscle stain golden brown, magnification × 100; 1b. (right) larger magnification (× 200).
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Figure 1: 1a. (left) Double immunostaining: tryptase positive mast cells (bright red) in a small airway in a tissue sample from a patient with moderate COPD (GOLD stage 2); bronchial and alveolar type 2 epithelial cells and smooth muscle stain golden brown, magnification × 100; 1b. (right) larger magnification (× 200).

Mentions: Immunohistochemistry was performed on 3 μm formalin fixed, paraffin embedded lung tissue sections. Consecutive tissue sections were stained for tryptase (AA1, DAKO, Glostrup, Denmark) and chymase (CC1, Abcam, Cambridge, UK) using an immuno-alkaline phosphatase method with goat-anti-mouse immunoglobulin conjugated to alkaline phosphatase as a second step and Fast Red/Napthol AS-Mx as a chromogen providing a bright red reaction product. Double staining was performed to delineate the different compartments. After chymase or tryptase staining, slides were incubated with a mixture of mouse monoclonal antibodies detecting anti-alpha-smooth-muscle actin (Progen, Heidelberg, Germany; clone ASM-1) and pan-keratin (AE1-AE3, Boehringer Mannheim, Mannheim, Germany). As a detection step, slides were incubated with rabbit anti-mouse immunoglobulin conjugated to peroxidase. 3'3'di-amino-benzidin together with H2O2 was used as a chromogen, providing a gold-brown reaction product. This double staining procedure with subsequent incubation steps allowed easy identification of mast cells with clear demarcation of smooth muscle area and delineation of bronchial epithelium, as well as outer limit of adventitia by (mainly type 2) alveolar epithelial cells (see figure 1 for illustration). Appropriate isotype matched control sera were used for negative controls.


Association of mast cells with lung function in chronic obstructive pulmonary disease.

Gosman MM, Postma DS, Vonk JM, Rutgers B, Lodewijk M, Smith M, Luinge MA, Ten Hacken NH, Timens W - Respir. Res. (2008)

1a. (left) Double immunostaining: tryptase positive mast cells (bright red) in a small airway in a tissue sample from a patient with moderate COPD (GOLD stage 2); bronchial and alveolar type 2 epithelial cells and smooth muscle stain golden brown, magnification × 100; 1b. (right) larger magnification (× 200).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2542362&req=5

Figure 1: 1a. (left) Double immunostaining: tryptase positive mast cells (bright red) in a small airway in a tissue sample from a patient with moderate COPD (GOLD stage 2); bronchial and alveolar type 2 epithelial cells and smooth muscle stain golden brown, magnification × 100; 1b. (right) larger magnification (× 200).
Mentions: Immunohistochemistry was performed on 3 μm formalin fixed, paraffin embedded lung tissue sections. Consecutive tissue sections were stained for tryptase (AA1, DAKO, Glostrup, Denmark) and chymase (CC1, Abcam, Cambridge, UK) using an immuno-alkaline phosphatase method with goat-anti-mouse immunoglobulin conjugated to alkaline phosphatase as a second step and Fast Red/Napthol AS-Mx as a chromogen providing a bright red reaction product. Double staining was performed to delineate the different compartments. After chymase or tryptase staining, slides were incubated with a mixture of mouse monoclonal antibodies detecting anti-alpha-smooth-muscle actin (Progen, Heidelberg, Germany; clone ASM-1) and pan-keratin (AE1-AE3, Boehringer Mannheim, Mannheim, Germany). As a detection step, slides were incubated with rabbit anti-mouse immunoglobulin conjugated to peroxidase. 3'3'di-amino-benzidin together with H2O2 was used as a chromogen, providing a gold-brown reaction product. This double staining procedure with subsequent incubation steps allowed easy identification of mast cells with clear demarcation of smooth muscle area and delineation of bronchial epithelium, as well as outer limit of adventitia by (mainly type 2) alveolar epithelial cells (see figure 1 for illustration). Appropriate isotype matched control sera were used for negative controls.

Bottom Line: In asthma, higher chymase positive mast cell (MC-C) numbers are associated with less airway obstruction.Numbers of MC-T and MC-C were determined in different regions of central and peripheral airways and percentage of degranulation was determined.In COPD, MC-T numbers in the airway wall and more specifically in the epithelium and subepithelial area of peripheral airways correlated positively with FEV1/VC (Spearman's rho (rs) 0.47, p = 0.05 and rs 0.48, p = 0.05, respectively); MC-C numbers in airway smooth muscle of peripheral airways correlated positively with FEV1% predicted (rs 0.57, p = 0.02).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pulmonology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands. margotgosman@hotmail.com

ABSTRACT

Background: In asthma, higher chymase positive mast cell (MC-C) numbers are associated with less airway obstruction. In COPD, the distribution of MC-C and tryptase positive mast cells (MC-T) in central and peripheral airways, and their relation with lung function, is unknown. We compared MC-T and MC-C distributions in COPD and controls without airflow limitation, and determined their relation with lung function.

Methods: Lung tissue sections from 19 COPD patients (median [interquartile range] FEV1% predicted 56 [23-75]) and 10 controls were stained for tryptase and chymase. Numbers of MC-T and MC-C were determined in different regions of central and peripheral airways and percentage of degranulation was determined.

Results: COPD patients had lower MC-T numbers in the subepithelial area of central airways than controls. In COPD, MC-T numbers in the airway wall and more specifically in the epithelium and subepithelial area of peripheral airways correlated positively with FEV1/VC (Spearman's rho (rs) 0.47, p = 0.05 and rs 0.48, p = 0.05, respectively); MC-C numbers in airway smooth muscle of peripheral airways correlated positively with FEV1% predicted (rs 0.57, p = 0.02). Both in COPD patients and controls the percentage of degranulated MC-T and MC-C mast cells was higher in peripheral than in central airways (all p < 0.05), but this was not different between the groups.

Conclusion: More MC-T and MC-C in peripheral airways correlate with better lung function in COPD patients. It is yet to determine whether this reflects a protective association of mast cells with COPD pathogenesis, or that other explanations are to be considered.

Show MeSH
Related in: MedlinePlus