INSULIN-LIKE-GROWTH-FACTOR BINDING-PROTEINS IN AIR-EXPOSED AND 85-PERCENT OXYGEN-EXPOSED ADULT-RAT LUNG

Expression of insulin-like growth factor (IGF) I and its type I recept or is increased in the adult rat lung exposed to 85% O-2. We hypothesi zed that there would be a parallel up-and downregulation of growth-sti mulating and growth-inhibiting IGF binding proteins (IGFBPs), respecti vely. The normal adult rat lung expresses mRNAs for IGFBP-2, -3, -4, - 5, and -6 but not for IGFBP-1. O-2 exposure for 6 or 14 days reduced I GFBP-3 and -6 and increased IGFBP-4 mRNA abundance. IGFBP-5 mRNA was r educed at 6 days but increased at 14 days. IGFBP-4 mRNA was localized to perivascular and peribronchial interstitial cells and IGFBP-5 mRNA to airway and alveolar epithelial cells. IGFBP-2, -4, and -5 immunoloc alized to airway epithelial cells in normal lung and to perivascular e xudates after 6 days in 85% O-2. IGFBP-2 was diffusely increased throu ghout the lung tissue only after a 6-day exposure. IGFBP-5 was reduced after a 6-day exposure but was increased and widely distributed after 14 days. IGFBP-4 increased over airway epithelium and subepithelial c ells after 6 days and over perivascular interstitial cells after 14 da ys of 85% O-2. These data are consistent with the predicted changes fo r IGFBPs on O-2 exposure except that the generally growth inhibitory I GFBP-4 was increased at sites of active cell proliferation.