Fetal lung cell-derived matrix alters distal lung epithelial ion transport

Extracellular matrix (ECM) synthesized by the fetal mesenchymal cells provides a supporting structure for the growing airways and is important for airway branching and in the differentiation of the primitive epithelium. We studied whether ECM, in addition to its structural role in lung interstitium, influences the ion transport of rat fetal distal lung epithelial cells (FDLE). FDLE monolayers were cultured on two different fetal mixed lung cell (MLC)-derived matrix preparations and studied in Ussing chambers. FDLE on MLC matrix had an increased resting equivalent short-circuit current (Ieq). Amiloride (10(-4) M apically) decreased the Ieq significantly in all the FDLE monolayers. The residual Ieq was significantly larger in FDLE grown on MLC matrix (increased by 150 and 80% under baseline and beta 2-agonist-stimulated conditions, respectively) than on control filters and filters coated with type I collagen, and type IV collagen, laminin, or fibronectin. The matrix produced by MLC isolated at an earlier gestational stage decreased the FDLE's sensitivity to amiloride. The increased amiloride-insensitive Ieq was only modestly affected by the Na+/K+/Cl- cotransport inhibitor bumetanide (10(-4) M basally) but was abolished when the [Cl-] of the bathing solution was reduced to 10 mM. These observations demonstrated that MLC elaborated ECM is able to change the nature of the ion transport of FDLE. ECM may be an important factor governing the ion transporting phenotype of fetal type II alveolar epithelial cells.