Effects of epidermal growth factor on alveolar epithelial
junctional permeability and active sodium transport.
Borok, Zea, Anooshiravan Hami, Spencer I. Danto, Richard L. Lubman,
Kwang-Jin Kim, and Edward D. Crandall.
Will Rogers Institute Pulmonary Research Center, Division of
Pulmonary and Critical Care Medicine, University of Southern
California, Los Angeles, CA 90033
APStracts 2:0207L, 1995.
The normal alveolar epithelium represents a resistant barrier to the
passive flux of fluid and solutes into the alveolar airspaces, and
actively reabsorbs sodium in a vectorial fashion. We evaluated the
effects of epidermal growth factor (EGF) on transepithelial
resistance (Rt) and active ion transport by alveolar epithelial cell
(AEC) monolayers on tissue culture-treated polycarbonate filters. Rat
type II cells were cultured in completely defined serum-free medium
(MDSF) or MDSF supplemented with EGF. The addition of EGF from either
day 0 or day 4 resulted in significant increases in Rt and short
circuit current (ISC) on day 5, with ED50 of 0.05 ng/ml and 0.1
ng/ml, respectively. Rt began to increase after 6 hr and became
maximal at 18 hr following the addition of EGF. The effect on ISC was
first observed at about 12 hr and peaked at 36 hr. Basolateral (but
not apical) EGF was responsible for these effects, which were
prevented by preincubation with tyrphostin RG 50864, a reversible
specific inhibitor of the EGF receptor tyrosine kinase. ISC decreased
with a sensitivity to apical inhibitors of sodium transport in the
order benzamil>amiloride>EIPA in MDSF +/- EGF, and was
completely inhibited by the addition of basolateral ouabain. Net
sodium flux and Na+,K+-ATPase activity both increased approximately
50% in the presence of EGF. These results indicate that EGF decreases
tight junctional permeability and increases active sodium transport
by AEC monolayers via basolaterally located EGF receptors. The
pathways for cellular sodium entry and exit (+/- EGF) are apical high
amiloride affinity sodium channels and basolateral sodium pumps.
These long-term effects of EGF on alveolar epithelial barrier
properties and transepithelial ion transport suggest that
pharmacologic interventions with this soluble factor may prove useful
for the management of alveolar edema.
Received 23 March 1995; accepted in final form 18 October 1995.
APS Manuscript Number L93-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95