The rat lung organotypic culture: an in vitro model for studying surfactant metabolism abnormalities.
The amount of surfactant present in the intra-alveolar space is mainly regulated by the synthesis and recycling of surfactant by type II pneumocytes. Biochemical analyses have shown that the surfactant level is frequently diminished and that protein-rich exudate can further interfere with surfactant function in the lungs of adult respiratory distress syndrome (ARDS) patients. The microenvironmental changes that occur in the alveoli of burned patients, who are prone to developing ARDS, are unclear. Therefore, using an in vitro rat lung organotypic culture, we showed that the sera of rats with a 3-day old, third-degree thermal injury (25-30% total body surface area) inhibited surfactant synthesis in organotypically cultured rat lung cells. Surfactant precursor, 3H-choline, incorporation into the surfactant was 58% of control. Using liposomes made of dipalmitoyl phosphatidylcholine and phosphatidylglycerol (8:1, v/v) or surfactant we showed that surfactant endocytosis by purified type II alveolar cells is an active, temperature-dependent process, and correlates with the quantity of surfactant present in the milieu. We also found that plasma protein-rich fluid interfered with surfactant endocytosis by the purified type II pneumocytes. These two processes of inhibition of surfactant synthesis and its reutilization by these cells may contribute to the pathogenesis of ARDS.
Li
J J
JJ
Department of Surgery, Shriners Burns Institute, Massachusetts General Hospital, Boston.
Bramlet
S G
SG
Carter
E A
EA
Burke
J F
JF
D000818:Animals; D002056:Burns / Q000097:blood / Q000378:metabolism; D002478:Cells, Cultured; D002794:Choline / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004705:Endocytosis; D008081:Liposomes; D008168:Lung / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000503:physiopathology / Q000648:ultrastructure; D011663:Pulmonary Surfactants / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D012128:Respiratory Distress Syndrome / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013395:Sucrose / Q000493:pharmacokinetics
D008081:Liposomes; D011663:Pulmonary Surfactants; D013395:Sucrose; D002794:Choline