Mechanisms of surfactant dysfunction in early acute lung injury.
Surfactant dysfunction that occurs during acute lung injury is associated with alterations in phospholipid, total protein, and surfactant apoprotein content. The functional importance of these changes was examined by characterizing the biophysical properties and biochemical composition of lung surfactant from endotoxin-treated guinea pigs (LPS) with acute lung injury. Static and dynamic lung compliance significantly decreased following endotoxin exposure. Lavage fluid demonstrated a neutrophil predominance, and tissue histopathology revealed inflammation consistent with acute lung injury. LPS surfactant isolated by ultracentrifugation had minimum surface tensions of 21 dynes/cm compared to 2 dynes/cm among control samples. Biochemical abnormalities in LPS surfactant included increased total protein, decreased phosphatidylcholine, and increased sphingomyelin, phosphatidylethanolamine, and lysophosphatidylcholine. The addition to normal guinea pig surfactant of butanol extracts precipitated from lavage fluid of LPS animals and containing known amounts of protein caused elevations in minimum surface tensions to > or = 20 dynes/cm at protein to phospholipid ratios equivalent to those observed in LPS surfactant pellets. Addition of equal amounts of precipitate isolated from control animals had no effect on interfacial properties. Furthermore, addition of lysophosphatidylcholine and sphingomyelin to normal surfactant to simulate composition changes observed in LPS surfactant had minimal effect on surface film behavior. The results support the hypothesis that aqueous soluble inhibitors of surfactant are generated within the alveolar compartment during acute inflammation, and that surfactant dysfunction cannot be accounted for on the basis of phospholipid composition changes.
Kennedy
M
M
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Phelps
D
D
Ingenito
E
E
D000818:Animals; D001696:Biomechanical Phenomena; D055592:Biophysical Phenomena; D001703:Biophysics; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D006168:Guinea Pigs; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D055370:Lung Injury; D008297:Male; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000378:metabolism*; D013500:Surface Tension
D008070:Lipopolysaccharides; D010743:Phospholipids; D011663:Pulmonary Surfactants