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

Abstract

Observationsin vivoin patients, supported by guinea-pigin vivodata, take centre stage in this perspective. Its objective is to highlight dichotomies between asthma features observedin vivoand 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 increasedin vivoin asthma. Such maintained barrier function in exudative asthma reflectsin vivoasymmetry of the epithelial lining as barrier between outside and inside world of molecules and cells. In desquamatory asthma, maintained epithelial tightness may be explained byin vivodemonstrations of exceedingly patchy epithelial loss, prompt creation of plasma-derived provisional barriers, and high-speed epithelial regeneration. Acknowledged protein/peptide secretion by epithelial cellsin vitrois contrasted here with a dominant, unidirectional movementin vivoof 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 observationsin vivoin asthmatics. Notions concerning activation/fate of mucosal tissue eosinophils illustrate additional distinctions between accepted views andin vivopatient observations. Finally,in vitro-based paradigms preaching defect epithelial regeneration and increased permeability in pathogenesis of asthma are contrasted with experimentalin vivoobservations of exaggerated epithelial regeneration, which is multipathogenic in its own right. In conclusion, unexpected and challengingin vivoobservations in recent decades underpin novel insights into mucosal mechanisms in asthma.