Cadmium transport through type II alveolar cell monolayers: contribution of transcellular and paracellular pathways in the rat ATII and the human A549 cells

Abstract

Cadmium (Cd) transport in alveolar type II (ATII) cells has been studied using two in vitro models widely used to investigate lung function: primary cultures of rat ATII cells and the human cell line A549. Nonlinear regression analyses of the uptake time-course of 109Cd revealed: a zero-time accumulation, a fast process of accumulation which proceeds within minutes, and a much slower process which takes hours. This three-step mechanism was characterized by different parameter values under dishes-or filter-growth conditions. A higher initial uptake rate ( v i) and equilibrium accumulation ( A max) of 109Cd were found in the rat ATII cells; these differences were not related to a higher level of adsorption onto the external surface of the cell membrane. Specific transport systems of similar capacity but different affinity (threefold higher in rat cells) were characterized. A significant transepithelial transport of 109Cd, with similar P coeff in both cell models, could not be exclusively related to cellular metal release. Results on 3H-mannitol permeability together with 109Cd efflux data strongly suggest a greater contribution of the paracellular pathways in Cd transport through A549 cell monolayers. These differences in transport properties between the two lung cell models may modify the dose–response curve for Cd toxicity.