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

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. Further, 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 is contrasted with experimental in-vivo observations of exaggerated epithelial regeneration, which is multi-pathogenic in its own right. Conclusion: unexpected and challenging in-vivo observations in recent decades underpin novel insights into mucosal mechanisms in asthma.