Differential Accumulation of Surfactant Protein A, B, and C mRNAs in Two Epithelial Cell Types of Hyperoxic Lung

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Abstract
The physiologic response of the lung to oxygen toxicity is complex, and similar among all mammals studied. Acute exposure to 100% O2 results in severe decreases in respiratory function and is accompanied by alterations in pulmonary surfactant metabolism, including the regulation of surfactant proteins A, B, and C (SP-A, SP-B, SP-C). Because surfactant proteins and their mRNAs can be expressed in alveolar epithelial type II cells, and nonciliated bronchial epithelial (Clara) cells, we were interested in determining if alterations in the abundance of SP-A, SP-B, and SP-C mRNAs occurred differentially in these two cell types during hyperoxic lung injury. Using quantitative in situ hybridization, we found that hyperoxic lung injury resulted in nearly 20-fold increases in SP-A and SP-B mRNAs in Clara cells, with relatively small (2-fold or less) increases in type II cells. Immunohistochemical analysis suggested a commensurate increase in SP-A protein in Clara cells. SP-C mRNA was only detected in type II cells, and changed little in hyperoxic lung. Because Clara cells are not known to produce surfactant, and appear to lack SP-C mRNA, these observations suggest that increased SP-A and SP-B may serve nonsurfactant functions in hyperoxic lung.