Pulmonary carbonic anhydrase IV: developmental regulation and cell-specific expression in the capillary endothelium

To investigate the pulmonary expression of membrane-associated carbonic anhydrase (CA IV), the full-length rat lung CA IV cDNA was isolated and characterized. The 1,205-bp cDNA was found to encode a 309-amino acid protein, including a 27-amino acid hydrophobic COOH-terminal extension, presumably cleaved prior to transfer of the protein to its glycosyl-phosphatidylinositol membrane anchor. The tissue-specific pattern of CA IV gene expression was found to be distinct from that of other CAs, with highest expression in lung, colon, kidney, brain, and heart. Pulmonary CA IV expression was found to be developmentally regulated, with a marked postnatal increase in mRNA content and immunoreactive protein concentration. CA IV localized by immunohistochemistry to the luminal side of the alveolar capillary endothelium, but was absent from endothelium of larger pulmonary vessels. Selective expression of CA IV in the alveolar capillaries provides evidence for specialized differentiation of this endothelial cell subpopulation and places CA IV in a strategic location to participate in carbon dioxide exchange and local pH regulation.