Intestinal epithelial secretion and barrier function: from bench to bedside

Abstract

Zusammenfassung. Grundlagen: Flüssigkeitssekre-tion und Barrierefunktion sind wichtige Eigenschaften des intestinalen Epithels. Die experimentellen Modelle, welche maßgeblich unser Verständnis für epitheliale Funktionen und ihre molekularen Mechanismen ermöglicht haben, sind vielen unbekannt.Methodik: Literaturübersicht experimenteller Studien über Grundlagen zur intestinalen Flüssigkeitssekretion und epithelialen Barrierefunktion.Ergebnisse: Ergebnisse von In-vitro-und In-vivo-Studien und deren Bedeutung für das Verständnis der intestinalen Elektrolyttransportmechanismen und der epithelialen Integrität werden diskutiert.Schlussfolgerungen: Experimentelle gastrointestinale Grundlagenforschung liefert Informationen von praktischklinischer Relevanz. Der gegenseitige "bench to bedside"-Dialog zwischen experimenteller und praktischer Medizin trägt wesentlich dazu bei, die den Erkrankungen zugrunde liegenden Prozesse besser zu verstehen und damit unsere Therapiekonzepte gastrointestinaler Erkrankungen zu verbessern.Schlüsselwörter: experimentelle Medizin, UssingKammer, T84-Zellen, Epithelintegrität, intestinale Sekretion.Summary. Background: Fluid secretion and the ability to form a barrier are critical functions of the intestinal epithelium. However, some clinicians may not have an understanding of the model systems that have been used to enhance our knowledge of these important epithelial functions and their molecular regulation.Methods: This article seeks to explain the basis of intestinal fluid secretion and barrier function, and modification of these processes in pathophysiological settings, by reviewing recent basic science literature.Results: Findings from studies conducted both in vivo and in vitro are discussed, with an emphasis on insights that have emerged by applying intestinal epithelial cell lines to investigations of electrolyte transport and the integrity of the epithelial barrier.Conclusions: Even basic observations in reductionist model systems can yield information that is of immediate and practical clinical relevance. Continued bidirectional "bench to bedside" dialogue may enhance the clinician's ability to intervene in gastrointestinal diseases.

Fatal Clostridium difficile-associated toxic megacolon following unrelated stem-cell transplantation

“…While these toxins exert some of the clinical effects of clostridium difficile, furthermore recent studies further indicate that biologic effects are also triggered by interactions of the rod on epithelial cells and via a mechanism involving nerve cells, neuropeptides (substance P, neurotensin), interleukin proteins, NF-kappa B, and immune cells, proteins and mediators released by these cells. These interactions activate a "neurohumoral" flush, which in turn results in destruction of the epithelial barrier thus enabling the development of systemic infection and sepsis [4].…”