Surface properties and sensitivity to protein-inhibition of a recombinant apoprotein C-based phospholipid mixture in vitro--comparison to natural surfactant.
Surfactant alterations due to protein leakage are implicated in the pathogenesis of the adult respiratory distress syndrome. In the present study, surface properties of a palmitic acid containing phospholipid mixture (DPPC: PG: PA/68.5:22.5:9) supplemented with 2% recombinant human surfactant apoprotein C (PLM-Crec) were compared to those of the lipids alone (PLM) and to those of calf lung surfactant extract (CLSE). Experiments were performed in a Wilhelmy balance and in a pulsating bubble surfactometer. Adsorption facilities and dynamic surface tension-lowering properties of the surfactants alone, their sensitivity to the inhibitory effect of fibrinogen (fbg), and their capacity to restore surface properties of fbg-inhibited CLSE were investigated. PLM revealed limited surface activity, was very sensitive to inhibition by fbg and had moderate effect on the surface properties of fbg-inhibited CLSE. In contrast, PLM-Crec and CLSE revealed similar excellent adsorption kinetics and dynamic surface tension lowering properties. Higher percentage of SP-C within the synthetic mixture (up to 10%) or additional admixture of human purified or recombinant SP-A (up to 10%) did not further improve these surface properties. However, PLM-Crec was markedly more sensitive to inactivation by fbg than CLSE. The surface activity of fbg-inhibited CLSE was fully restored by additional admixture of CLSE or PLM-Crec in both the Wilhelmy and the bubble system, with slight superiority of the natural surfactant extract. We conclude that the surface properties of PLM-Crec are clearly superior to those of the apoprotein-free lipid mixture and are similar to those of the natural surfactant extract CLSE. PLM-Crec is markedly more sensitive to inhibition by fibrinogen than CLSE, but possesses nearly equivalent efficacy in restoring the surface properties of fbg-inhibited CLSE as compared to the natural material.
Seeger
W
W
Department of Internal Medicine, Justus-Liebig-University Giessen, F.R.G.
Thede
C
C
Günther
A
A
Grube
C
C
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000327:Adsorption; D000595:Amino Acid Sequence; D001056:Apolipoproteins C / Q000737:chemistry / Q000378:metabolism*; D005340:Fibrinogen / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000737:chemistry*; D011510:Proteolipids / Q000737:chemistry / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013499:Surface Properties; D013500:Surface Tension
D001056:Apolipoproteins C; D010169:Palmitic Acids; D011510:Proteolipids; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D015060:1,2-Dipalmitoylphosphatidylcholine; D019308:Palmitic Acid; D005340:Fibrinogen