CELL-SPECIFIC ALTERATIONS IN EXPRESSION OF HYPEROXIA-INDUCED MESSENGER-RNAS OF LUNG

Hyperoxic lung injury is an unfortunate consequence of ventilatory oxygen therapy that is necessary to sustain life in certain clinical situations. The biochemical events that accompany hyperoxia of the lung, and the molecular mechanisms underlying these events, are incompletely understood. To better understand hyperoxic lung injury, our laboratory has cloned a set of genes corresponding to mRNAs that increase in abundance in the lungs of hyperoxic rabbits. In this report, we focus on three hyperoxia-induced cDNA clones, which encode surfactant apoprotein A (SP-A), the tissue inhibitor of metalloproteinases (TIMP), and metallothionein. In situ hybridizations and RNA dot blots of isolated lung cell populations indicate that the abundance of mRNA encoding all three proteins is increased by hyperoxia in specific cell types. SP-A mRNA increases in type II alveolar epithelial cells and in bronchiolar epithelial cells. TIMP mRNA increases in interstitial fibroblasts, in chondrocytes of the cartilage surrounding airways, and in endothelial cells of a specific subset of vessels, probably venules. Metallothionein transcripts also increase in chondrocytes and pulmonary fibroblasts. A comparison of the increase in these mRNAs during hyperoxic exposure in adults and newborns indicates that adults respond faster and to a greater extent than newborns and suggests that the rate and extent of these increases is correlated with the time course and severity of the injury.