Effects of a surfactant-associated protein and calcium ions on the structure and surface activity of lung surfactant lipids.
Previous studies have demonstrated that lung-specific proteins are associated with surfactant lipids, particularly the highly surface active subfraction known as tubular myelin. We have isolated a surfactant-associated protein complex with molecular weight components of 36 000, 32 000, and 28 000 and reassembled it with protein-free lung surfactant lipids prepared as small unilamellar liposomes. The effects of divalent cations on the structure and surface activity of this protein-lipid mixture were investigated by following (1) the state of lipid dispersion by changes in turbidity and by electron microscopy and (2) the ability of the surfactant lipids to form a surface film from an aqueous subphase at 37 degrees C. The protein complex markedly increased the rate of Ca2+-induced surfactant-lipid aggregation. Electron microscopy demonstrated transformation of the small unilamellar liposomes (median diameter 440 A) into large aggregates. The threshold Ca2+ concentration required for rapid lipid aggregation was reduced from 13 to 0.5 mM by the protein complex. This protein-facilitated lipid aggregation did not occur if Mg2+ was the only divalent cation present. Similarly, 5 mM Ca2+ but not 5 mM Mg2+ improved the ability of the protein-lipid mixture to form a surface film at 37 degrees C. Extensive aggregation of the surfactant lipids without protein by 20 mM Ca2+ or 20 mM Mg2+ did not promote rapid surface film formation. These results add to the growing evidence that specific Ca2+-protein-lipid interactions are important in determining both the structure and function of extracellular lung surfactant fractions.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004285:Dogs; D004492:Edetic Acid / Q000494:pharmacology; D007700:Kinetics; D008081:Liposomes; D008168:Lung / Q000378:metabolism*; D008854:Microscopy, Electron; D010743:Phospholipids / Q000302:isolation & purification / Q000378:metabolism*; D011312:Pressure; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000302:isolation & purification / Q000378:metabolism*; D013499:Surface Properties
D008081:Liposomes; D010743:Phospholipids; D011506:Proteins; D011663:Pulmonary Surfactants; D004492:Edetic Acid; D002118:Calcium