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Uncontrolled asthmatics have increased FceRI+ and TGF-β–positive MCTC mast cells and collagen VI in the alveolar parenchyma

Andersson, C. K. LU ; Weitoft, M. LU ; Rydell-Törmänen, K. LU ; Bjermer, L. LU ; Westergren-Thorsson, G. LU and Erjefält, J. S. LU (2018) In Clinical and Experimental Allergy 48(3). p.266-277
Abstract

Background: Asthma has been associated with increased collagen deposition in both conducting airways and alveolar parenchyma. Mast cells (MCs) are key effector cells in asthma and have the ability to affect collagen synthesis. However, the link between clinical control and changes in bronchial and alveolar MC phenotypes and specific collagens in controlled and uncontrolled asthma remains unknown. Objective: To investigate MC phenotypes in correlation with deposition of specific collagen subtypes in patients with controlled and uncontrolled asthma as well as to healthy controls. Methods: The tissue expression of IgE+, FcεRI+ and TGF-β+ MCs, as well as immunoreactivity of collagen I, III and VI, was... (More)

Background: Asthma has been associated with increased collagen deposition in both conducting airways and alveolar parenchyma. Mast cells (MCs) are key effector cells in asthma and have the ability to affect collagen synthesis. However, the link between clinical control and changes in bronchial and alveolar MC phenotypes and specific collagens in controlled and uncontrolled asthma remains unknown. Objective: To investigate MC phenotypes in correlation with deposition of specific collagen subtypes in patients with controlled and uncontrolled asthma as well as to healthy controls. Methods: The tissue expression of IgE+, FcεRI+ and TGF-β+ MCs, as well as immunoreactivity of collagen I, III and VI, was assessed using immunohistochemistry on bronchial and transbronchial biopsies from controlled asthmatics (n = 9), uncontrolled asthmatics (n = 16) and healthy controls (n = 8). Results: In the alveolar parenchyma, the total number of MCs, as well as the number of FcεRI+ MCs and pro-fibrotic TGF-β+ MCTC, was significantly increased in uncontrolled asthma compared to both controlled asthma and healthy controls. The proportion of TGF-β+ MCTC correlated positively to an increased immunoreactivity of alveolar collagen VI but not collagen I and III. Collagen VI was increased in the alveolar parenchyma of uncontrolled asthmatics compared to controlled asthmatics. Controlled asthmatics had an increased deposition of alveolar collagen I. In bronchi, the immunoreactivity of collagen I was increased in both controlled and uncontrolled asthmatics while collagen III was increased only in controlled asthmatics. Conclusions: Patients with uncontrolled atopic asthma have an altered pro-fibrotic MCTC phenotype in the alveolar parenchyma that is associated with alveolar collagen VI. The present data thus support distal lung mast cell and matrix changes as histopathological features of asthma that may be of particular clinical relevance in patients who have remaining symptoms despite conventional inhaler therapy.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
alveolar, asthma, collagen, mast cell, remodelling, TGF-b
in
Clinical and Experimental Allergy
volume
48
issue
3
pages
12 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:85042059792
ISSN
0954-7894
DOI
10.1111/cea.13092
language
English
LU publication?
yes
id
94cf8384-1ae9-45c5-8882-72e5b07e6447
date added to LUP
2018-03-17 19:09:18
date last changed
2018-10-28 13:48:51
@article{94cf8384-1ae9-45c5-8882-72e5b07e6447,
  abstract     = {<p>Background: Asthma has been associated with increased collagen deposition in both conducting airways and alveolar parenchyma. Mast cells (MCs) are key effector cells in asthma and have the ability to affect collagen synthesis. However, the link between clinical control and changes in bronchial and alveolar MC phenotypes and specific collagens in controlled and uncontrolled asthma remains unknown. Objective: To investigate MC phenotypes in correlation with deposition of specific collagen subtypes in patients with controlled and uncontrolled asthma as well as to healthy controls. Methods: The tissue expression of IgE<sup>+</sup>, FcεRI<sup>+</sup> and TGF-β<sup>+</sup> MCs, as well as immunoreactivity of collagen I, III and VI, was assessed using immunohistochemistry on bronchial and transbronchial biopsies from controlled asthmatics (n = 9), uncontrolled asthmatics (n = 16) and healthy controls (n = 8). Results: In the alveolar parenchyma, the total number of MCs, as well as the number of FcεRI<sup>+</sup> MCs and pro-fibrotic TGF-β<sup>+</sup> MC<sub>TC,</sub> was significantly increased in uncontrolled asthma compared to both controlled asthma and healthy controls. The proportion of TGF-β<sup>+</sup> MC<sub>TC</sub> correlated positively to an increased immunoreactivity of alveolar collagen VI but not collagen I and III. Collagen VI was increased in the alveolar parenchyma of uncontrolled asthmatics compared to controlled asthmatics. Controlled asthmatics had an increased deposition of alveolar collagen I. In bronchi, the immunoreactivity of collagen I was increased in both controlled and uncontrolled asthmatics while collagen III was increased only in controlled asthmatics. Conclusions: Patients with uncontrolled atopic asthma have an altered pro-fibrotic MC<sub>TC</sub> phenotype in the alveolar parenchyma that is associated with alveolar collagen VI. The present data thus support distal lung mast cell and matrix changes as histopathological features of asthma that may be of particular clinical relevance in patients who have remaining symptoms despite conventional inhaler therapy.</p>},
  author       = {Andersson, C. K. and Weitoft, M. and Rydell-Törmänen, K. and Bjermer, L. and Westergren-Thorsson, G. and Erjefält, J. S.},
  issn         = {0954-7894},
  keyword      = {alveolar,asthma,collagen,mast cell,remodelling,TGF-b},
  language     = {eng},
  month        = {03},
  number       = {3},
  pages        = {266--277},
  publisher    = {Wiley-Blackwell},
  series       = {Clinical and Experimental Allergy},
  title        = {Uncontrolled asthmatics have increased FceRI<sup>+</sup> and TGF-β–positive MC<sub>TC</sub> mast cells and collagen VI in the alveolar parenchyma},
  url          = {http://dx.doi.org/10.1111/cea.13092},
  volume       = {48},
  year         = {2018},
}