Interaction of an artificial surfactant in human pulmonary epithelial cells.
Surfaxin (lucinactant), a peptide-based surfactant consisting of dipalmitoylphosphatidylcholine (DPPC) plus KL(4) (sinapultide) (a synthetic peptide modeled after human surfactant protein-B), is effective in treating respiratory distress syndrome in preterm infants. Our goal was to determine the uptake and effects of Surfaxin on human pulmonary type II cells isolated from fetal tissue and other lung cell types. Based on previous published reports, we hypothesized that this exogenous synthetic surfactant would have little effect on type II cell surfactant-related physiological features. Human type II cells and A549 and NCI-H441 adenocarcinoma cells incorporated (3)H-KL(4) and (14)C-DPPC components in Surfaxin, but with different kinetics. Fractionation of NCI-H441 and A549 cellular components indicated that the highest specific activity of (3)H-KL(4) was present in the 18,000g cellular fraction (which contains vesicles and lysosomes). The number of lamellar bodies (LBs) appears to increase in human type II cells incubated in the presence of Surfaxin when visualized by light microscopy, while LB structure (determined by electron microscopy) was not altered. Expression of endogenous surfactant protein (SP-A, SP-B, and SP-C) mRNA levels in human type II cells was not altered by the presence of Surfaxin. We conclude that while human type II cells and other lung cell types can incorporate the components of Surfaxin, the surfactant-related physiological functions of these cells are not altered.
Romero
Edgar J
EJ
Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Health Science Center-Houston, Houston, TX, USA.
Moya
Fernando R
FR
Tuvim
Michael J
MJ
Alcorn
Joseph L
JL
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000493:pharmacokinetics*; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D015152:Blotting, Northern; D020126:Brefeldin A / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000737:chemistry; D004338:Drug Combinations; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007424:Intracellular Fluid / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008854:Microscopy, Electron; D015388:Organelles / Q000187:drug effects / Q000648:ultrastructure; D010455:Peptides / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000493:pharmacokinetics*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020545:Respiratory Mucosa / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*
D016895:Culture Media, Serum-Free; D004338:Drug Combinations; D036341:Intercellular Signaling Peptides and Proteins; C097558:KL4 surfactant; D010455:Peptides; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D012333:RNA, Messenger; C113283:sinapultide; D020126:Brefeldin A; D015060:1,2-Dipalmitoylphosphatidylcholine