Surfactant protein A regulates surfactant phospholipid clearance after LPS-induced injury in vivo.
Previous in vitro studies have suggested that surfactant protein A (SP-A) may play a role in pulmonary surfactant homeostasis by mediating surfactant secretion and clearance. However, mice made deficient in SP-A [SP-A (-/-) animals] have relatively normal levels of surfactant compared with wild-type SP-A (+/+) animals. We hypothesize that SP-A may play a role in surfactant homeostasis after acute lung injury. Bacterial lipopolysaccharide was instilled into the lungs of SP-A (-/-) mice and SP-A (+/+) mice to induce injury. Surfactant phospholipid levels were increased 1.6-fold in injured SP-A (-/-) animals, although injury did not alter [3H]choline or [14C]palmitate incorporation into dipalmitoylphosphatidylcholine (DPPC), suggesting no change in surfactant synthesis/secretion 12 h after injury. Clearance of [3H]DPPC from the lungs of injured SP-A (-/-) animals was decreased by approximately 40%. Instillation of 50 microg of exogenous SP-A rescued both the clearance defect and the increased phospholipid defect in injured SP-A (-/-) animals, suggesting that SP-A may play a role in regulating clearance of surfactant phospholipids after acute lung injury.
Quintero
Omar A
OA
Department of Cell Biology, Duke University, Durham, North Carolina 27710, USA.
Korfhagen
Thomas R
TR
Wright
Jo Rae
JR
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism*; D000818:Animals; D002794:Choline / Q000493:pharmacokinetics; D006706:Homeostasis / Q000502:physiology*; D008070:Lipopolysaccharides; D008081:Liposomes / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010168:Palmitates / Q000493:pharmacokinetics; D011510:Proteolipids / Q000235:genetics* / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics* / Q000378:metabolism*; D014316:Tritium
D008070:Lipopolysaccharides; D008081:Liposomes; D010168:Palmitates; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D014316:Tritium; D015060:1,2-Dipalmitoylphosphatidylcholine; D002794:Choline