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

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.