Permeability Properties of an In Vitro Model of the Alveolar Epithelium

Cell culture models of epithelial barriers in the body are widely used to study the permeation of nutrients, drugs, infectious agents and pollutants into the body tissues and circulation. The NCI-H441 cell line cultured at the air-liquid interface mimics certain phenotypic and functional characteristics of the human alveolar epithelium. Here the permeability properties of the NCI-H441 model were characterised and compared against published data using experimental measurements and mathematical modelling. Cells were cultured under air-liquid interface conditions and trans-epithelial electrical resistance (TEER) and apparent permeability (Papp) to sodium fluorescein (MW 383 Da) and fluorescently labelled dextrans (MW 4000–150,000 Da) was measured. It was found that TEER was independent of cell seeding density while Papp decreased with higher seeding density and plateaued beyond a density of 500,000 cells/cm2. Using the framework of functional pore analysis, a mathematical model was fitted to Papp values measured in this work as well as previously published datasets from human cell lines and primary human and rat cells. It was found that the air-liquid interface NCI-H441 model most closely matched the primary cell line results in contrast to published data using A549 and liquid-interface NCI-H441 cell cultures, supporting the use of this model to study the permeability of the alveolar epithelium to large molecules.