AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 5 762-L771, Copyright © 1995 by American Physiological Society
Fetal lung cell-derived matrix alters distal lung epithelial ion transport
O. M. Pitkanen, A. K. Tanswell and H. M. O'Brodovich
Medical Research Council Group in Lung Development, Hospital for Sick Children's Research Institute, Toronto, Ontario, Canada.
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.
