The epidermal growth factor receptor (egfr) network in type 2
pneumocytes exposed to hyperoxia in vitro.
Nici, Linda, Maria Medina, A. Raymond Frackelton.
Department of Internal Medicine, Roger Williams Medical Center and
Brown University, Providence, Rhode Island, 02908
APStracts 2:0157L, 1995.
Hyperoxia is a well characterized model of injury and repair of the
lung. Type 1 cell damage is followed by type 2 cell proliferation and
differentiation which restores normal structure and function. The
Epidermal Growth Factor receptor (EGFR) network is known to be a
potent modulator of epithelial cell growth. Here we examine the EGFR
network on isolated rat type 2 cells and SV40T-T2, a type 2 cell
line, under normoxic conditions, after 24 and 48 hrs of in vitro
hyperoxia, and after 24 hrs of normoxic recovery. EGF induces
tyrosine phosphorylation of EGFRs in type 2 cells and SV40T-T2 cells
which decreases with hyperoxia and increases above normoxic levels in
recovering cells, suggesting biphasic changes in receptor number or
function with injury. The EGFR appears to be stimulated in an
autocrine fashion in these cells. There is decreased DNA synthesis
and proliferation in SV40T-T2 and isolated type 2 cells treated with
tyrphostin B56, a specific EGFR inhibitor. Pretreatment with suramin,
which binds to growth factor, results in increased EGFR tyrosine
phosphorylation after stimulation, suggesting disruption of normal
autocrine receptor downregulation. We have also identified TGF
-[alpha] in conditioned media (CM) from normoxic and hyperoxic SV40T
-T2 and type 2 cells. Finally, we show increased EGF-bioactivity in
both bronchoalveolar lavage (BAL) from hyperoxic rats and conditioned
media (CM) from hyperoxic cells as compared to normoxic controls.
These findings support an integral role for an autocrine EGFR network
in the type 2 cell response to injury.
Received 19 September 1994; accepted in final form 21 August
1995.
APS Manuscript Number L277-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.