Cell line A549: a model system for the study of alveolar type II cell function.

Abstract

Cell line A549, a continuously cultured line derived from a human pulmonary adenocarcinoma that has morphologic and biochemical features of the pulmonary alveolar type II cell, was studied with regard to saturated phosphatidylcholine synthesis and secretion. Evaluation of a number of culture media showed that those media that supported the most rapid rate of in vitro growth were least optimal for saturated phosphatidylcholine synthesis. Similarly, a labeled precursor (choline labeled with tritium) was most efficiently converted to saturated phosphatidylcholine when growth was slow or arrested, whereas during phases of active cellular proliferation a greater proportion was incorporated into unsaturated (structural) phosphatidylcholine. De novo synthesis of phosphatidylcholine was primarily via the cytidine diphosphate-choline pathway, because no incorporation of labeled methyl groups from S-adenosyl-L-methionine was observed. Cortisol stimulated tritium-labeled choline incorporation into saturated phosphatidylcholine in a manner that likely involed a steroid receptor system, whereas cortisone was inactive. The half-life of cellular saturated phosphatidylcholine was of the order of 100 hours and could be accounted for virtually entirely by release of this phospholipid into the medium unchanged. Both cholinergic and adrenergic agents in high doses modestly stimulated the release of pre-labeled saturated phosphatidylcholine from the cells, and the response to these secretagogues was significantly enhanced by cortisol. Cell line A 549 promises to be a useful model system for studies of the cellular events involved in pulmonary saturated phosphatidylcholine synthesis and secretion.