AJP - Lung Cellular and Molecular Physiology, Vol 267, Issue 6 720-L727, Copyright © 1994 by American Physiological Society
Oxygen-induced changes in protein synthesis and cell proliferation in cultured lung slices
P. S. Shapiro, F. E. Casty, W. S. Stirewalt, K. O. Leslie, M. P. Absher and J. N. Evans
Department of Molecular Physiology and Biophysics, University of Vermont College of Medicine, Burlington 05405.
Elevated fractions of inspired O2 induce significant remodeling of the
airways and vasculature of the lung. The present study was undertaken to
determine the direct effects of altered levels of O2 on protein synthesis
and cell proliferation in lung tissue cultured in vitro. Rat lungs were
inflated with low-melt agarose, cut transversely into 1-mm sections, and
cultured in a serum-free medium for up to 7 days in the presence of 10, 21,
40, or 70% O2. Tissue structure integrity was maintained as assessed by
light and electron microscopy. Fractional synthesis rates (FSR,
%protein/day) of soluble protein from cultured lung homogenates
demonstrated an O2 concentration-dependent response. Tissue cultured in the
presence of 70% O2 exhibited the highest FSR. The FSR of tissue cultured in
21 or 40% O2 did not differ and demonstrated FSR values greater than tissue
cultured in 10% O2. Cell proliferation was assessed histologically in
parenchymal gas-exchange regions of lung slices cultured in the presence of
5-bromo-2'-deoxyuridine. Labeling indexes for tissue cultured in 21, 40, or
70% indicated an O2-dependent increase in cell proliferation after 3 days
in culture followed by a return to baseline levels after 7 days. Tissue
cultured in the presence of 10% O2 showed no change in cell proliferation
over time. The data indicate a direct influence of O2 on lung cell growth
and proliferation. Additionally, these studies show that this in vitro
model may be suitable for further understanding of the mechanistic basis
involved in proliferative events during lung injury.
