Bronchoalveolar Lavage Lipids during Development of Bleomycin-induced Fibrosis in Rats: Relationship to Altered Epithelial Cell Morphology

Abstract

Alterations in the structure and function of alveolar epithelial cells may contribute to the interstitial fibrosis that can develop following lung injury. The present studies were undertaken to determine if alterations observed in alveolar epithelial cell morphology and cytoskeletal composition are reflected in the profile of bronchoalveolar lavage (BAL) lipids recovered from injured lung. BAL protein and lipid analyses were performed on fluids recovered from control rats and from rats 7, 14, and 28 days after intratracheal instillation of bleomycin, an antineoplastic agent well-known to cause pulmonary interstitial fibrosis. There were increases in recovery of total protein, nonpolar lipid, polar lipid, and phospholipid following bleomycin treatment. The recovery of saturated phosphatidylcholine was increased, but recovery of a second surfactant phospholipid, phosphatidylglycerol, was unchanged, resulting in a significant change in their ratio. The recoveries of cholesterol, cholesterol ester, and triglyceride also were elevated. Changes in the proportional recoveries of neutral lipids, such as cholesterol and saturated phospholipids, could partly explain concurrent reductions in lung compliance that have been described. Changes in lavage lipids paralleled both the process of alveolar reepithelialization and altered expression of alveolar epithelial cell cytoskeletal proteins. Changes in lipid metabolism by alveolar epithelial cells following bleomycin-induced lung injury may be responsible for altered lavage lipid recovery and may directly be related to processes that take place during alveolar type II cell hyperplasia followed by transition to type I cells. BAL lipid analyses thus may provide a relatively noninvasive way of assessing these events.