EFFECTS OF EGF ON ALVEOLAR EPITHELIAL JUNCTIONAL PERMEABILITY AND ACTIVE SODIUM-TRANSPORT

We evaluated the effects of epidermal growth factor (EGF) on transepit helial resistance (R(t)) and active ion transport by alveolar epitheli al cell (AEC) monolayers on tissue culture-treated polycarbonate filte rs. Rat type II cells were cultured in completely defined serum-free m edium (MDSF) or MDSF supplemented with EGF. The addition of EGF from e ither day 0 (chronic) or day 4 (subacute) resulted in significant incr eases in R(t) and short-circuit current (I-sc) on day 5. After subacut e exposure, these effects were delayed in onset by 6-12 h and sustaine d for > 24 h. Basolateral (but not apical) EGF was responsible for the se effects, which were prevented by preincubation with tyrphostin RG-5 0864, a reversible specific inhibitor of the EGF receptor tyrosine kin ase. I-sc decreased, with a sensitivity to apical inhibitors of sodium transport in the order benzamil > amiloride > 5-(N-ethyl-N-isopropyl) amiloride in MDSF +/- EGF, and was completely inhibited by the additio n of basolateral ouabain. Net sodium flux and Na+,K+-ATPase activity b oth increased similar to 50% in the presence of EGF. These results ind icate that 1) EGF decreases tight junctional permeability and increase s active sodium transport by AEC monolayers via basolaterally located EGF receptors, and 2) the pathways for AEC sodium entry and exit (+/- EGF) are apical high amiloride affinity sodium channels and basolatera l sodium pumps.