DEVELOPMENTAL REGULATION OF PHOSPHOLIPID SECRETION BY FETAL TYPE-II PNEUMOCYTES

Surfactant sufficiency is dependent upon adequate synthesis and secret ion of surfactant by the type II alveolar epithelium. Our laboratory h as previously shown that basal secretion of surfactant phospholipid by differentiated fetal type II cells is lower than the basal secretion by adult cells. The purposes of this study were to determine if undiff erentiated fetal type II cells can secrete phosphatidylcholine, to det ermine if terbutaline, a beta-adrenergic agonist, stimulates secretion of surfactant phospholipids by undifferentiated fetal cells and to ex amine the effects of differentiation on secretion of surfactant phosph olipids by fetal cells. Constitutive (basal) secretion of phosphatidyl choline increased linearly as a function of time in both undifferentia ted and differentiated cells, but the rate of secretion was greater in differentiated cells than the rate of secretion in undifferentiated c ells. Terbutaline caused a concentration-dependent increase in secreti on in both undifferentiated and differentiated cells. Maximal effectiv e concentration and EC(50) were similar for undifferentiated (10(-6) M , 0.2 mu M) and differentiated (10(-5) M, 0.3 mu M) cells, The relativ e stimulation of secretion above control values was greater for undiff erentiated cells. The kinetics of terbutaline stimulation varied signi ficantly with cellular differentiation. Terbutaline resulted in 230% s timulation of secretion in undifferentiated cells at 30 min followed b y a decline in the response to terbutaline at 60 to 120 min. In contra st, terbutaline stimulated secretion by differentiated cells showed a sustained linear increase 0 to 120 min. This regulation of stimulated secretion is not present in undifferentiated cells. We conclude that u ndifferentiated type II cells are capable of the secretion of phosphat idylcholine and that terbutaline stimulates secretion by undifferentia ted cells. Furthermore, basal secretion increases as a function of dif ferentiation of type II cells and the regulation of stimulated secreti on seen in differentiated cells is not developed in undifferentiated c ells. The developmental regulation of the secretion of surfactant is c omplex and probably involves both excitatory as well as inhibitory mec hanisms which develop at different stages of differentiation of the ty pe II cell.