INSULIN-LIKE GROWTH-FACTOR-I AND TYPE-I INSULIN-LIKE GROWTH-FACTOR RECEPTOR IN 85-PERCENT O-2-EXPOSED RAT LUNG

The expression of insulin-like growth factor I (IGF-I) and insulinlike growth factor II (IGF-II) was studied in the lungs of adult rats expo sed to air or 85% O-2, using Northern analysis, in situ hybridization, and immunohistochemistry. Distribution of the type I insulin-like gro wth factor receptor (IGF-IR) was assessed by immunohistochemistry. IGF -I, but not IGF-II, was localized to airway epithelium, while IGF-IR w as localized to perivascular and peribronchial cells, in the lungs of animals breathing air. IGF-II mRNA did not increase with exposure to 8 5% O-2, but IGF-II was localized to sites of perivascular edema and to occasional peribronchial cells. A widespread increase in IGF-I mRNA a nd peptide was seen after both a 6-day and a 14-day exposure to O-2, W ith maximal expression in the airway and alveolar epithelium, and less er expression in interstitial cells. After 6 days in 85% O-2, increase d IGF-IR immunoreactivity was localized to both perivascular and perib ronchial cells and to endothelial cells. By 14 days in 85% O-2, IGF-IR immunoreactivity was also localized to alveolar epithelial cells. The distribution of IGF-IR immunoreactivity was consistent with a paracri ne role for IGF-I in O-2-mediated pulmonary hypertension and airway hy perreactivity, by mediating smooth muscle cell hyperplasia, as well as a role in endothelial cell repair and late pneumocyte hyperplasia. Th e relative insensitivity of IGF-IR immunohistochemistry did not allow us to identify cells with low abundance IGF-IR, and potential cellular targets for IGF-I actions after O-2-exposure may be even more extensi ve than those recognized here.