In Vitro Models of the Tracheo-Bronchial Epithelium

Abstract

The lung is composed of two major anatomically distinct regions: the conducting airways (tracheo-bronchial region) and the gas-exchanging airspaces (alveolar region). The conducting airways can be further subdivided into the trachea plus larger bronchi and the distal bronchiolar airways. Each of these regions consists of distinct types of epithelial cells with unique phenotypes, morphologies and associated physiological functions. This chapter focuses on various model systems that have been utilised to study drug transport and metabolism in the adult tracheo-bronchial epithelium. This includes primary cell cultures, airway cell lines and culture systems with or without the cystic fibrosis gene deletion. The permeability of increasing numbers of compounds in these drug absorption models has been reported. Cell culture systems are particularly amenable to the study of transport mechanisms and the expression of a variety of active transport mechanisms in airway cell culture systems is summarised. Another application of epithelial cell models is to predict drug absorption in vivo. The drug metabolising capacity of electrically tight and non-barrier forming airway cell models is also summarised in terms of the P450, phase II enzymes plus peptidase and protease activity.