Related Experiment Videos
Developmental changes in phosphatidylinositol transfer protein concentration and phospholipid transfer activities in
1Department of Pediatrics, University of Maryland School of Medicine, Baltimore 21201, USA. rviscard@umaryland.edu
Insights
Phospholipid transfer proteins (PLTPs) are crucial for lung development. This study reveals their dynamic changes in type II cells during gestation and birth, highlighting their role in surfactant metabolism.
Area of Science:
- Biochemistry
- Cell Biology
- Pulmonary Medicine
Background:
- Phospholipid transfer proteins (PLTPs) facilitate phospholipid movement between membranes.
- Type II cells are critical for lung surfactant production and function.
Purpose of the Study:
- To investigate phospholipid transfer protein alpha (PITP alpha) concentration and activity in type II cells versus whole lung.
- To examine developmental changes in PITP alpha and phospholipid transfer activities during late gestation and the newborn period.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) for PITP alpha quantification.
- Vesicle-rat lung membrane transfer assay for phospholipid transfer activity.
- Immunodepletion assays to identify contributing PLTPs.
Main Results:
- PITP alpha concentration increased in fetal type II cells, declining postnatally, but was not enriched in adult type II cells compared to whole lung.
- Phospholipid transfer activities, particularly for phosphatidylglycerol (PG), were significantly enriched in adult type II cell cytosol.
- Transfer activities showed marked developmental increases in late gestation, with PG, PI, and PC transfer rates exceeding adult levels.
- PITP alpha depletion did not significantly alter transfer activities, indicating other PLTPs are primary drivers.
Conclusions:
- While PITP alpha levels fluctuate developmentally, other PLTPs are the main contributors to phospholipid transfer in type II cells.
- Developmental changes in PLTPs correlate with surfactant phospholipid metabolism, suggesting a key role in type II cell function.
- These findings provide insights into the molecular mechanisms governing lung maturation and surfactant homeostasis.
Abstract:
The phospholipid transfer proteins (PLTPs) are cytosolic proteins that have been characterized by their ability to facilitate the transfer of phospholipids between membranes in vitro. The goals of this study were to determine whether PITP alpha concentration and phospholipid transfer activities are enriched in type II cells compared with whole lung and to determine the developmental changes in PITP alpha concentration and phospholipid transfer activities during late gestation and newborn period. The concentration of PITP alpha in type II cell cytosol measured by enzyme-linked immunosorbent assay (ELISA) increased during late fetal gestation to 2.2-fold adult levels and declined 41% during the first postnatal day. However, compared to whole adult lung cytosol, type II cell cytosol was not significantly enriched with PITP alpha. Phospholipid transfer activities were determined by a vesicle-rat lung membrane transfer assay. In adult lung, transfer activities for all the phospholipids were enriched in adult type II cell cytosol compared to whole lung cytosol (phosphatidylglycerol [PG], 12.5-fold; phosphatidylinositol [PI], 9.2-fold; phosphatidylcholine [PC], 6.5-fold; and phosphatidylethanolamine [PE], 6.6-fold; P < .05 in each case). The rate of phospholipid transfer in type II cell cytosol increased during late fetal gestation to levels 4.9 (PG), 3.7 (PI), and 2.8 (PC) times greater than adult levels. In cytosol from cells from different stages, the order of transfer rate was PG > PI > PC > PE. PITP alpha immunodepletion of adult type II cytosol did not significantly affect phospholipid transfer activities, suggesting that other PLTPs are responsible for the majority of the observed transfer activities in these cells. Developmental increases in PITP alpha concentration and other PLTPs parallel developmental changes in type II cell surfactant phospholipid metabolism, suggesting a possible role of these transfer proteins in the unique function of the type II cell.