© 2008 American Thoracic Society
Carbonic Anhydrase and Alveolar Fluid Absorption
Harbor UCLA, Medicine To the Editor: The recent article by Chen and coworkers (1) reports that carbonic anhydrase II (CAII) is found in both type I and type II alveolar epithelial cells. Although inhibition of CAII with acetazolamide or methazolamide delayed intracellular acidification during hypercapnia in cultured cells, it did not slow reabsorption of fluid from isolated-perfused rat lungs during hypercapnia. The authors appear to have overlooked our earlier study in Science (2), cited in the article by Crandall and O'Brassky (3), which provided direct evidence for carbonic anhydrase in rabbit lungs perfused without red cells. We found that conversion of H14CO3– to 14CO2 in the pulmonary vasculature was rapid and inhibited by intravascular acetazolamide. However, we subsequently reported that conversion of H14CO3– to 14CO2 in fluid introduced into the airspaces is slow (unless CA is added to the airway fluid) and is not influenced by airspace acetazolamide (4). This suggests that although CAII, as well as membrane-bound forms of CA such as CA IV, VI, and XIV (5, 6), may be expressed within the pulmonary epithelial cells, they are not detectable on the apical surface of the pulmonary epithelium, at sites accessible to fluid lining the airways. Nor could we find evidence for CA on the outer surface of red cells (7). In contrast, CA activity does appear to be very abundant on the pulmonary endothelial surface facing the plasma (2, 4). The deficiency of CA activity on the apical surfaces of the pulmonary epithelium should be considered in interpreting the observation of Chen and colleagues (1) that CA inhibitors do not influence epithelial transport of fluid in the rat lung. Even in the absence of CA inhibitors, CO2/HCO3– disequilibria in the airway fluid could influence local pH and epithelial function. Footnotes Conflict of Interest Statement: The author does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. References
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