Oxygen-induced changes in protein synthesis and cell proliferation in cultured lung slices

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.