Circulating Factors That Modify Lung Cell DNA Synthesis Following Exposure to Inhaled Oxidants. III. Effect of Plasma on Lung Pneumocyte and Fibroblast DNA Synthesis Following Exposure of Adult Rats to 85% Oxygen

Abstract

Previous studies, in which adult rats were exposed to 1 ppm ozone for 2 weeks, demonstrated the appearance in plasma of separate factors that stimulated DNA synthesis by cultured pneumocytes and lung fibroblasts in a dose-dependant and cell-specific fashion. Both factors had isoelectric points of 6.45–6.75, but differed by molecular mass. The pneumocyte factor had an estimated weight of 38 ± 3 kDa, while the fibroblast factor had an estimated molecular weight of 32 ± 2 kDa. To determine whether the appearance of these factors in plasma is specific for ozone injury or whether they appear in response to other oxidant injuries, adult rats were exposed to 85% O2 or air for up to 2 weeks. Animals were sacrificed at 3, 5, 7, or 14 days after the onset of exposure. Plasma samples were subjected to sequential preparative electrofocusing and high-performance liquid chromatography (HPLC). Heat-inactivated plasma fractions, with an isoelectric point of 6.45–6.75, contained a factor of 32 ± 2 kDa, which enhanced lung fibroblast DNA synthesis at a single time point on day 5 of 85% O2 exposure, and a factor of 38 ± 3 kDa, which enhanced pneumocyte DNA synthesis on days 5, 7, and 14 of 85% O2 exposure. Of the known growth factors, those most likely to have these physical characteristics are platelet-derived growth factor (PDGF) and insulin-like growth factor-1. Additional groups of animals were exposed to air or 85% O2 for 5 days for plasma collection. Animals exposed to 85% O2 had a 60% increase of plasma immunoreactive PDGF and a 90% increase of plasma immunoreactive IGF-1, compared with values for control animals exposed to air.