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.

Translation of in vitro findings to patients with asthma: a timely and compelling challenge

“…In his challenging perspective in this issue of the European Respiratory Journal [5], Carl Persson argues that findings from in vivo observations in asthma are often overlooked, because of the dominance of in vitro pathogenetic research based on cell culture, studies of isolated cell populations and molecular biology approaches. Without any doubt, the title of his perspective ("In vivo observations provide insight into roles of eosinophils and epithelial cells in asthma") is absolutely correct.…”

“…Without any doubt, the title of his perspective ("In vivo observations provide insight into roles of eosinophils and epithelial cells in asthma") is absolutely correct. PERSSON [5] uses various examples to argue that multiple concepts in asthma pathogenesis have been established, without paying attention to what actually can be observed in vivo. He specifically focuses on observations in patients and studies in guinea pigs providing evidence for plasma exudation into the airways, eosinophil cytolysis and epithelial cell loss.…”

“…He specifically focuses on observations in patients and studies in guinea pigs providing evidence for plasma exudation into the airways, eosinophil cytolysis and epithelial cell loss. PERSSON [5] argues that plasma-derived rather than epithelial-derived molecules may be essential for providing defence and repair molecules to the epithelial surface of the lung in health and asthma. The work of C. Persson and his co-workers in Lund in Sweden has indeed provided evidence that plasma exudation may be a non-injurious physiological process that provides protection of epithelial surfaces [6].…”

“…Various forms of regulated cell death have been identified in the lung (and other organs), including not only apoptosis, but also necroptosis, pyroptosis and autophagy (recently reviewed by SAULER et al [9]). PERSSON [5] argues that there is no in vivo evidence for eosinophil apoptosis in airway tissues, whereas there is evidence for cytolysis. In vitro studies have clearly provided evidence for apoptosis of eosinophils and supported the role of this process in asthma pathogenesis [10,11].…”

“…In his perspective, PERSSON [5] also provides other interesting examples of apparent clashes between concepts partly based on in vitro studies and in vivo observations. In vivo studies in patients, healthy controls or in animals allow the performance of experiments using whole, live organisms, whereas in vitro experiments are performed in a controlled environment outside such an organism.…”