Iprindole reverses the lamellar body deficiency of cultured L-2 cells. Possible implications in the reversal of surfactant deficiency.
Type II alveolar epithelial cells in long-term culture typically lose the ability to synthesize surfactant together with a loss of the characteristic lamellar bodies in the cytoplasm of the cells. Iprindole, a cationic amphiphilic drug, induces lamellar body formation in cultured L-2 cells, a cell line derived from rat Type II cells, but devoid of lamellar bodies. With concentrations of 10(-7)-10(-5) M iprindole, which approximate therapeutic plasma concentrations in human subjects, the drug induced the formation of lamellar bodies within 8 hours of incubation. This effect on cell morphology was rapidly lost after withdrawal of the drug. At concentrations of iprindole which induced lamellar body formation, there was a significant increase in phospholipid content of the L-2 cells as well as an increase in disaturated phosphatidylcholine, an important constituent of surfactant. These studies suggest that the use of drugs such as iprindole may represent a novel approach in the augmentation of phospholipid (and possibly surfactant) content of Type II cells in the lung.
Martin
W J
WJ
Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.
Kachel
D L
DL
D000818:Animals; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D002479:Inclusion Bodies / Q000187:drug effects* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D007488:Iprindole / Q000494:pharmacology* / Q000633:toxicity; D010743:Phospholipids / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011663:Pulmonary Surfactants / Q000172:deficiency / Q000378:metabolism
D007211:Indoles; D010743:Phospholipids; D011663:Pulmonary Surfactants; D007488:Iprindole