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In vivo observations provide insight into roles of eosinophils and epithelial cells in asthma

Carl Persson
European Respiratory Journal 2019 54: 1900470; DOI: 10.1183/13993003.00470-2019
Carl Persson
Laboratory Medicine University Hospital, Lund, Sweden
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  • For correspondence: carl.persson@med.lu.se
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Abstract

Observations in vivo in patients, supported by guinea-pig in vivo data, take centre stage in this perspective. Its objective is to highlight dichotomies between asthma features observed in vivo and accepted views involving cell/molecular biology research paradigms. For example, increased bronchial epithelial permeability is now considered a major paradigm and trait of asthma, yet, absorption of inhaled tracers has not been increased in vivo in asthma. Such maintained barrier function in exudative asthma reflects in vivo asymmetry of the epithelial lining as barrier between outside and inside world of molecules and cells. In desquamatory asthma, maintained epithelial tightness may be explained by in vivo demonstrations of exceedingly patchy epithelial loss, prompt creation of plasma-derived provisional barriers, and high-speed epithelial regeneration. Acknowledged protein/peptide secretion by epithelial cells in vitro is contrasted here with a dominant, unidirectional movement in vivo of plasma-derived proteins/peptides (including antimicrobial peptides) to the surface of an intact epithelial lining. Furthermore, longstanding claims that epithelium-produced adenosine is a mediator of asthma are eroded by observations in vivo in asthmatics. Notions concerning activation/fate of mucosal tissue eosinophils illustrate additional distinctions between accepted views and in vivo patient observations. Finally, in vitro-based paradigms preaching defect epithelial regeneration and increased permeability in pathogenesis of asthma are contrasted with experimental in vivo observations of exaggerated epithelial regeneration, which is multipathogenic in its own right. In conclusion, unexpected and challenging in vivo observations in recent decades underpin novel insights into mucosal mechanisms in asthma.

Abstract

Exploratory in vivo research approaches produce unexpected discoveries and novel understanding independent of currently accepted paradigms http://bit.ly/2YgLdnF

Footnotes

  • Conflict of interest: C. Persson has nothing to disclose.

  • Received March 5, 2019.
  • Accepted June 18, 2019.
  • Copyright ©ERS 2019
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Vol 54 Issue 4 Table of Contents
European Respiratory Journal: 54 (4)
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In vivo observations provide insight into roles of eosinophils and epithelial cells in asthma
Carl Persson
European Respiratory Journal Oct 2019, 54 (4) 1900470; DOI: 10.1183/13993003.00470-2019

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In vivo observations provide insight into roles of eosinophils and epithelial cells in asthma
Carl Persson
European Respiratory Journal Oct 2019, 54 (4) 1900470; DOI: 10.1183/13993003.00470-2019
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  • Article
    • Abstract
    • Abstract
    • Introduction
    • Widened aspects of airway epithelium and eosinophils in asthma
    • Absorption of inhaled molecules is not increased in asthma patients, not even in asthma caused by epithelium-toxic chemicals; are these data enough to erode the current idea of increased epithelial permeability as a paradigm of pathogenesis of asthma?
    • Inflammatory stimulus-induced acute airways plasma exudation: to what extent is this associated with increased absorption-permeability of the epithelial lining?
    • Antimicrobial peptides and major defence and repair proteins on the surface of an intact bronchial mucosa in vivo: are they components of plasma exudation or produced by local airway cells?
    • Resolution of airway eosinophilic inflammation: elimination of eosinophils through apoptosis/phagocytosis that occurs in vitro, or epithelial transmission that occurs in vivo?
    • Cytolysis of eosinophils and occurrence of clusters of free eosinophil granules: is this an artefact or a major mode of eosinophil activation in vivo?
    • Highly active plasma-derived barriers over a denuded, but intact, basement membrane cater for safe and speedy epithelial regeneration in vivo: might exaggerated epithelial regeneration, rather than the current paradigm of defect repair, characterise asthma?
    • Micrographs illustrating extensive denudation may reflect areas with numerous tiny denudation spots; is patchy epithelial sloughing key to maintained mucosal tightness in vivo in asthma?
    • Pathogenesis of asthma: exaggerated epithelial regeneration rather than increased permeability?
    • Anti-asthma drugs and proposed mediators of asthma emanating from stressed epithelium: is the claimed role of adenosine eroded by in vivo observations in asthma?
    • Select early contributions to our understanding of asthma and its treatment may not have received due attention; tribute to Salter and Solis-Cohen
    • How can research paradigms thrive in the face of contradictory in vivo observations?
    • Conclusion
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