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Am J Physiol Lung Cell Mol Physiol 274: L647-L656, 1998;
1040-0605/98 $5.00
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Vol. 274, Issue 4, L647-L656, April 1998

Insulin-like growth factor binding proteins in air- and 85% oxygen-exposed adult rat lung

Robin N. N. Han1, Victor K. M. Han2, Shilpa Buch1, Bruce A. Freeman3, Martin Post1, and A. Keith Tanswell1

1 Medical Research Council Group in Lung Development, Hospital for Sick Children Research Institute and Department of Paediatrics, University of Toronto, Toronto, Ontario M5S 1A8; 2 Medical Research Council Group in Fetal and Neonatal Health and Development, Lawson Research Institute, St. Joseph's Health Centre and Departments of Paediatrics, Anatomy, and Biochemistry, University of Western Ontario, London, Ontario, Canada N6A 4V2; and 3 Departments of Anesthesiology, Biochemistry, and Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama 35294

Expression of insulin-like growth factor (IGF) I and its type I receptor is increased in the adult rat lung exposed to 85% O2. We hypothesized that there would be a parallel up- and downregulation of growth-stimulating and growth-inhibiting IGF binding proteins (IGFBPs), respectively. The normal adult rat lung expresses mRNAs for IGFBP-2, -3, -4, -5, and -6 but not for IGFBP-1. O2 exposure for 6 or 14 days reduced IGFBP-3 and -6 and increased IGFBP-4 mRNA abundance. IGFBP-5 mRNA was reduced 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 immunolocalized to airway epithelial cells in normal lung and to perivascular exudates after 6 days in 85% O2. IGFBP-2 was diffusely increased throughout 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 cells after 6 days and over perivascular interstitial cells after 14 days of 85% O2. These data are consistent with the predicted changes for IGFBPs on O2 exposure except that the generally growth-inhibitory IGFBP-4 was increased at sites of active cell proliferation.

pulmonary oxygen toxicity; cell interactions; lung injury


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