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Modulation of alveolar type II cell differentiated function in vitro.
J M Shannon1, S D Jennings, L D Nielsen
1Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado.
The American Journal of Physiology
|April 1, 1992
Summary
Alveolar type II cells lose function when flattened on culture surfaces. Detaching these cells from the surface reversed this loss, showing cell differentiation is reversible and depends on cell structure.
Area of Science:
- Cell Biology
- Pulmonary Medicine
- Biochemistry
Background:
- Adult rat alveolar type II cells lose differentiated function when cultured on surfaces promoting cell spreading.
- This loss of function is often considered a permanent phenotypic change in vitro.
Purpose of the Study:
- To investigate if the loss of differentiated function in cultured rat alveolar type II cells is a reversible process.
- To determine the role of the culture substratum and cell architecture in maintaining alveolar type II cell differentiation.
Main Methods:
- Culturing adult rat alveolar type II cells on attached (flattening) or floating (non-flattening) collagen gels with fibroblast feeder layers.
- Evaluating markers of differentiation including surfactant protein mRNA expression (SP-A, SP-B, SP-C), phospholipid biosynthesis, protein synthesis, and cell morphology.
- Assessing the reversibility of functional loss by detaching cells from attached gels after 4 days and culturing them on floating gels for an additional 4 days.
Main Results:
- Cells cultured on attached collagen gels showed a loss of differentiated function.
- Detaching the gels after 4 days of culture on attached collagen gels led to a significant recovery of differentiated characteristics.
- Markers of differentiation, including surfactant protein mRNA levels and phospholipid biosynthesis, were restored upon changing the culture environment.
Conclusions:
- The loss of differentiated function in adult rat alveolar type II cells cultured on a substratum promoting cell spreading is a reversible phenotypic change.
- Cellular architecture and the culture environment play critical roles in modulating alveolar type II cell differentiation.
- These findings highlight the importance of normal cell architecture for normal cell function and suggest potential for in vitro studies of type II cell differentiation and potential type I cell progression.