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. 2022 Sep 26;11(9):e1417.
doi: 10.1002/cti2.1417. eCollection 2022.

Increased mast cell activation in eosinophilic chronic obstructive pulmonary disease

Andrew Higham  1 , Josiah Dungwa  2 , Tuyet-Hang Pham  3 , Christopher McCrae  3 , Dave Singh  1   2
Affiliations

Increased mast cell activation in eosinophilic chronic obstructive pulmonary disease

Andrew Higham et al. Clin Transl Immunology. .

Abstract

Objectives: A subset of chronic obstructive pulmonary disease (COPD) patients have increased numbers of airway eosinophils associated with elevated markers of T2 inflammation. This analysis focussed on mast cell counts and mast cell-related gene expression in COPD patients with higher vs lower eosinophil counts.

Methods: We investigated gene expression of tryptase (TPSAB1), carboxypeptidase A3 (CPA3), chymase (CMA1) and two mast cell specific gene signatures; a bronchial biopsy signature (MCbb) and an IgE signature (MCIgE) using sputum cells and bronchial epithelial brushings. Gene expression analysis was conducted by RNA-sequencing. We also examined bronchial biopsy mast cell numbers by immunohistochemistry.

Results: There was increased expression of TPSAB1, CPA3 and MCbb in eosinophilhigh than in eosinophillow COPD patients in sputum cells and bronchial epithelial brushings (fold change differences 1.21 and 1.28, respectively, P < 0.01). Mast cell gene expression was associated with markers of T2 and eosinophilic inflammation (IL13, CLCA1, CST1, CCL26, eosinophil counts in sputum and bronchial mucosa; rho = 0.4-0.8; P < 0.05). There was no difference in MCIgE gene expression between groups. There was no difference in the total number of bronchial biopsy mast cells between groups.

Conclusion: These results demonstrate that eosinophilic inflammation is associated with altered mast cell characteristics in COPD patients, implicating mast cells as a component of T2 inflammation present in a subset of COPD patients.

Keywords: eosinophils; epithelial cells; sputum; type 2 inflammation.

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Conflict of interest statement

DS has received sponsorship to attend and speak at international meetings, honoraria for lecturing or attending advisory boards from the following companies: Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Pulmatrix, Sanofi, Teva, Theravance and Verona. AH and JD have no conflicts of interest. T‐HP and CM are employees of AstraZeneca.

Figures

Figure 1
Figure 1
Bronchial brushing mast cell gene expression in eosinophillow and eosinophilhigh chronic obstructive pulmonary disease (COPD) patients. RNA‐sequencing was used to examine the expression of (a) TPSAB1, (b) CPA3, (c) CMA1, (d) MCbb signature and (e) MCIgE signature in n = 17 eosinophillow and n = 20 eosinophilhigh COPD patients. Data are presented as individual values where the black horizontal line represents the mean (a–c) or median (d and e).
Figure 2
Figure 2
Correlations between bronchial brushing mast cell gene expression and T2 biomarkers. RNA‐sequencing was used to examine correlations between the MCbb signature and (a) chronic obstructive pulmonary disease (COPD) T2 signature, (b) blood eosinophils, (c) sputum eosinophils and (d) bronchial biopsy eosinophilsin n = 17 eosinophillow and n = 20 eosinophilhigh COPD patients. Data were analysed by Spearman's correlation.
Figure 3
Figure 3
Bronchial brushing mast cell gene expression in inhaled corticosteroids (ICS) users and non‐users. RNA‐sequencing was used to examine the expression of (a) TPSAB1, (b) CPA3, (c) CMA1, (d) MCbb signature and (e) MCIgE signature in n = 25 ICS users (ICS Yes) and n = 12 non‐users (ICS No). Data are presented as individual values where the black horizontal line represents the mean (a–c) or median (d).
Figure 4
Figure 4
Mast cell quantification in bronchial biopsies. The number of subepithelial tryptase+ (MT), tryptase+chymase+ (MTC) and the total number of mast cells (MT + MTC) were quantified by immunofluorescence (a, b) and the number of intra‐epithelial tryptase+ mast cells were quantified by immunohistochemistry (c). Representative images of immunofluorescence where green and orange arrows indicate MT and MTC cells respectively (d) and immunohistochemistry where white arrows indicate tryptase‐positive mast cells (e). Comparisons were made between eosinophillow vs eosinophilhigh patients (a) n = 10 vs n = 13; (c) n = 14 vs n = 15; ICS users vs non‐users (b) n = 16 vs n = 7. P‐values in b signify differences between the same mast cell populations in ICS Yes vs ICS No groups.
Figure 5
Figure 5
Sputum mast cell gene expression in eosinophillow and eosinophilhigh COPD patients. RNA‐sequencing was used to examine the expression of (a) MCbb signature and correlations between the MCbb signature and (b) COPD T2 signature, (c) blood eosinophils and (d) sputum eosinophils in n = 11 eosinophillow and n = 15 eosinophilhigh COPD patients. Data are presented as individual values where the black horizontal line represents the median (a). Data are analysed by Spearman's correlation (b–d).
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References

    1. Higham A, Quinn AM, Cancado JED, Singh D. The pathology of small airways disease in COPD: historical aspects and future directions. Respir Res 2019; 20: 49. - PMC - PubMed
    1. Rutgers SR, Postma DS, ten Hacken NH et al. Ongoing airway inflammation in patients with COPD who do not currently smoke. Thorax 2000; 55: 12–18. - PMC - PubMed
    1. Rutgers SR, Timens W, Kaufmann HF, van der Mark TW, Koeter GH, Postma DS. Comparison of induced sputum with bronchial wash, bronchoalveolar lavage and bronchial biopsies in COPD. Eur Respir J 2000; 15: 109–115. - PubMed
    1. Higham A, Leow‐Dyke S, Jackson N, Singh D. Stability of eosinophilic inflammation in COPD bronchial biopsies. Eur Respir J 2020; 56: 2004167. - PubMed
    1. Kolsum U, Damera G, Pham TH et al. Pulmonary inflammation in patients with chronic obstructive pulmonary disease with higher blood eosinophil counts. J Allergy Clin Immunol 2017; 140: 1181–1184.e7. - PubMed