THE LUNG is a complex organ that contains at least 40 different varieties of cells. Different types of pulmonary parenchymal cells were first identified based on their histological characteristics (7). Subsequently, it has become possible to isolate individual populations of pulmonary cells to allow the investigation of their cellular and molecular biological characteristics. Relatively pure populations of type II alveolar epithelial cells have been isolated from a number of species and provide an important tool for understanding the biology of the alveolar space (9, 16, 20). In particular, these cell preparations have been used successfully for the elucidation of the pathways involved in the synthesis, secretion, and recycling of pulmonary surfactant (15, 25). However, when maintained under standard cell culture conditions (adherent to tissue culture-treated plastic in medium supplemented with fetal bovine serum), type II cells undergo a well-characterized series of changes in which they lose many of the specific features of the type II cell phenotype (2, 9). At the same time, these cells acquire certain morphological and antigenic features characteristic of type I alveolar epithelial cells in vivo (2, 4, 8, 10, 11). A number of investigators have used these isolated alveolar epithelial cells to study aspects of alveolar epithelial biology that are independent of pulmonary surfactant. However, questions have been raised concerning the identity of these cells and their relevance as tools for the study of alveolar epithelial cell biology. Are these type II cells, or type I cells, or merely cells that have nonspecifically dedifferentiated in tissue culture? We argue that type II cell-derived cultures, when appropriately used, can provide important in vitro systems for the study of many different aspects of alveolar epithelial cell biology, including issues that are related to the biology of type I cells. This commentary is not intended as a general review of alveolar epithelial cell differentiation, nor is it to serve as a catalogue of the culture conditions that may affect epithelial cell phenotype. Instead, we intend to address the relevance of alveolar epithelial cell cultures as models of lung cell biology and to promote a discussion of these issues within the community of investigators studying the alveolar epithelium. Broader recognition that the information derived from these epithelial cell cultures can be of value will advance our knowledge of alveolar epithelial cell biology.

Cellular phenotype is a consequence of the expression of a number of different specific genes generating functional capacities and spatial relationships. While some regulatory factors may influence a collection of cellular properties simultaneously, it is now clear that phenotypic characteristics often are regulated independently. For example, by altering culture conditions, liver or mammary epithelial cells can be induced to express varying collections of tissue-specific protein products (18). Similarly, with appropriate manipulation of culture conditions, isolated rat type II alveolar epithelial cells can express a subset of the characteristics manifested by type II cells in vivo (14, 24, 26, 27). These cells can be induced to synthesize and secrete surfactant apoprotein A but not surfactant apoprotein D. Under these conditions, they do not synthesize significant amounts of the surfactant component phosphatidylglycerol, a specific characteristic of type II cells, despite producing abundant disaturated phosphatidylcholine (for review see Ref. 2). Similarly, the expression of cell surface molecules such as glyoproteins recognized by specific lectins (2) or intercellular adhesion molecule 1 (associated with normal type I cells)(23) may be controlled separately from the …