EPIDERMAL GROWTH-FACTOR INCREASES LUNG LIQUID CLEARANCE IN RAT LUNGS

Epidermal growth factor (EGF) has been reported to stimulate the proli feration of epithelial cells and increase Na+ flux and Na+-K+-ATPase f unction in alveolar epithelial cell monolayers. Increases in Na+-K+-AT Pase in alveolar type II cells (AT2) have been associated with increas ed active Na+ transport and lung edema clearance across the rat alveol ar epithelium in a model of proliferative lung injury. Thus we tested whether administration of aerosolized EGF to rat lungs would increase active Na+ transport and lung liquid clearance. Sixteen adult Sprague- Dawley male rats were randomized to three groups. To a group of six ra ts, an aerosol generated from 20 mu g of EGF in saline was delivered t o the lungs, to a second group of five rats only aerosolized saline wa s delivered, and a third group of five rats without treatment served a s the control. Forty-eight hours postaerosolization of rat lungs with EGF there was an similar to 40% increase in active Na+ transport and l ung liquid clearance compared with control rats, in the absence of cha nges in Na-22(+), [H-3]mannitol, and albumin permeabilities. The Na+-K +-ATPase activity in AT2 cells harvested from these lungs was increase d in rats that received aerosolized EGF compared with AT2 cells from b oth control rats and rats receiving aerosolized saline. These results support the hypothesis that in vivo delivery of EGF aerosols upregulat es alveolar epithelial Na+-K+-ATPase and increases lung liquid clearan ce in rats.