CIRCULATING FACTORS THAT MODIFY LUNG-CELL DNA-SYNTHESIS FOLLOWING EXPOSURE TO INHALED OXIDANTS .3. EFFECT OF PLASMA ON LUNG PNEUMOCYTE AND FIBROBLAST DNA-SYNTHESIS FOLLOWING EXPOSURE OF ADULT-RATS TO 85-PERCENT OXYGEN

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-dependent 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.