Abstract
Erythropoietin has a wide variety of nonhematopoietic effects in the body, including the regulation of important enzymatic activity in the pulmonary endothelium. If erythropoietin plays a role in lung vascular cell function, we hypothesized that it might play a similar role in respiratory epithelial cell function. We used the A549 cell, an immortal adenocarcinoma cell line that has features similar to Type II alveolar cells, to test the effect of erythropoietin (50 U/ml) on growth and ion transport activity. Erythropoietin increased total cell protein in monolayers of A549 cells by an average of 30 % (n = 6, control: 47+ 10 vs erythropoietin 62+ 3, mean+ SD, ph 0.05), an effect that was largely the result of an increase in cell number and not simply cell hypertrophy (n = 6, control: 1.5 million+ 0.4 vs erythropoietin 2.2 million+ 0.4, ph 0.05). To see if erythropoietin also modulated ion transport in these cells, we measured the accumulation of 22Na and efflux of 36Cl following a 24 h erythropoietin exposure in monolayer. Total sodium uptake was increased on average by 30% (n = 10, control: 214+ 128 nmol/mg protein vs erythropoietin 278+ 169, p < 0.05), an effect that was the result predominately of an increase in transport through amiloride-sensitive sodium channels (n = 10, control: 180+ 122 nmol/mg protein vs erythropoietin 238+ 159, p < 0.05), the sodium transport pathway linked to fluid removal in the distal airspace. In related studies we measured the effect of a 24 h exposure to erythropoietin on the rate of 36Cl efflux from these same cells. Chloride efflux activity is linked to fluid secretion into the lung lumen, an important respiratory epithelial cell function before birth. We found erythropoietin decreased 36Cl efflux on average by nearly 40% (n = 6, control: 3.6+ 1.1 nmol/mg protein/min vs erythropoietin 2.2+ 0.9, p < 0.05). These results suggest that erythropoietin might play a role in the growth and function of the respiratory epithelium of the distal lung. Because of the influence of erythropoietin on sodium and chloride transport, we speculate that erythropoietin might influence fluid clearance from the alveolar space.
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DeYoung, P., Kapur, A., Lichtman, M. et al. 9 Effects of Erythropoietin on Respiratory Epithelial Cell Growth and Function.. Pediatr Res 58, 817 (2005). https://doi.org/10.1203/00006450-200510000-00039
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DOI: https://doi.org/10.1203/00006450-200510000-00039