© 2008 American Thoracic Society
Carbonic Anhydrase and Alveolar Fluid Absorption
Northwestern University Feinberg School of Medicine From the Authors: We appreciate the comment by Dr. Effros on our article "Carbonic anhydrase II and alveolar fluid reabsorption during hypercapnia" (1). We found that although both type I and type II alveolar epithelial cells (AEC) types expressed carbonic anhydrase II (CAII), it appears that the carbonic anhydrase activity (CA) is not important in the regulation of alveolar fluid reabsorption (AFR) in hypercapnic conditions. We have recently described that lungs exposed to high PCO2 have decreased AFR associated with decreased Na,K-ATPase function (2, 3); thus, we set out to study the role that carbonic anhydrase (enzyme that catalyses the conversion of CO2 to H+ and HCO3–) played in AFR. We perfused isolated fluid–filled rat lungs with a solution containing 40 or 60 mm Hg CO2 and observed that AFR was reduced approximately 50% in hypercapnic conditions, which was not inhibited by acetazolamide or methazolamide. We measured intracellular pH in cultured cells exposed to high CO2 using it as a marker of CAII activity as previously described (4), and although we agree with Dr. Effros that some of the changes in pH might be due by the CO2/HCO3– disequilibria, we clearly found significant inhibition in the presence of CA inhibitors. We agree that the Overton's rule applies in that the permeability coefficient of a solute is linearly related to its oil–water partition coefficient but, we recognize also that the permeability of membranes to CO2 does not always obey the solubility-diffusion model (5). However, in our article (1) we did not focus on the mechanisms of CO2 transport across epithelial cells. In our report, lungs were perfused from the endothelial side with the hypercapnic solution and PCO2 was equilibrated in the airspaces after 10 minutes. We should have cited the elegant article by Effros and colleagues (6), which is an important contribution and sheds light into this issue. We are aware that there is no CAII in the apical side of the AEC; indeed, we took this into consideration when performing our experiments, in which the high pCO2 was perfused via the pulmonary circulation and CO2 levels were in equilibrium before the assessment of the AFR. The conclusion of our manuscript that CA activity does not affect the hypercapnia-induced AFR inhibition is not contradictory with the fact that there might not be apical CAII in AEC. We believe that high CO2 levels generate an intracellular signaling cascade independent of pH (2, 3), that regulates alveolar epithelial Na,K-ATPase function and AFR. Footnotes Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the manuscript. References
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