UP-REGULATION OF ALVEOLAR EPITHELIAL FLUID TRANSPORT AFTER SUBACUTE LUNG INJURY IN RATS FROM BLEOMYCIN

Alveolar epithelial fluid transport was studied 10 days after subacute lung injury had been induced with intratracheal bleomycin (0.75 U). A n isosmolar Ringer lactate solution with 5% bovine serum albumin and I -125-labeled albumin as the alveolar protein tracer was instilled into the right lung; the rats were then studied for either 1 or 4 h. Alveo lar fluid clearance was increased in bleomycin-injured rats by 110% ov er 1 h and by 75% over 4 h compared with control rats (P < 0.05). The increase in alveolar fluid clearance was partially inhibited by amilor ide (10(-3) M). Alveolar fluid clearance decreased toward normal level s in rats that were studied 60 days after bleomycin instillation. Rema rkably, the measured increase in net alveolar fluid clearance occurred in the presence of a significant increase in alveolar epithelial perm eability to protein. Moreover, the increase in alveolar epithelial flu id clearance occurred even though the mRNA for the ol-subunit of the e pithelial sodium channel was decreased in alveolar epithelial type II cells isolated from these rats. In addition, Na-22 uptake by isolated alveolar epithelial type II cells from rats treated with bleomycin dem onstrated a 52% decrease in uptake compared with type II cells from co ntrol rats. Morphological results demonstrated a significant hyperplas ia of alveolar type II epithelial cells 10 days after bleomycin injury . Thus, these results provide evidence that proliferation of alveolar epithelial type II cells after acute lung injury may upregulate the tr ansport capacity of the alveolar epithelium, even though the expressio n of epithelial sodium channels is reduced and the uptake of 22Na per cell is also reduced. These results may have clinical relevance for th e resolution of alveolar edema in the subacute phase of lung injury.