Differential sensitivity to fibrinogen inhibition of SP-C- vs. SP-B-based surfactants.
Inhibition of surfactant function by plasma-derived proteins is assumed to occur under conditions of alveolar protein leakage. We investigated surface properties and sensitivity to the inhibitory capacity of fibrinogen (Fbg) of artificial surfactants in a pulsating-bubble surfactometer. Phospholipid-fatty acid mixtures (PLM) with or without hydrophobic apoproteins [natural bovine surfactant proteins (SP) B and C, recombinant human SP-C] were used. Without Fbg, all apoprotein-based surfactants exhibited rapid absorption facilities and reduced surface tension to near zero values under dynamic compression. Fbg caused a dose-dependent reduction of adsorption kinetics and dynamic surface tension-lowering properties of all surfactant preparations, but there was a marked rank order of "Fbg sensitivity": PLM without apoprotein being the most sensitive and SP-B-based PLM the least. Fbg sensitivity of recombinant SP-C-based PLM could be lowered dose dependently by adding small amounts of SP-B. For further support of a putative role of SP-B in resistance to Fbg inhibition, calf lung surfactant extract was incubated with monoclonal antibody against SP-B. Without Fbg, anti-SP-B had little influence. However, sensitivity to the inhibitory effect of Fbg was markedly and dose dependently increased by anti-SP-B but not by control immunoglobulin. We conclude that SP-B-based surfactant preparations display markedly lower susceptibility to Fbg inhibition than SP-C combinants.
Seeger
W
W
Department of Internal Medicine, Justus-Liebig-University Giessen, Federal Republic of Germany.
Günther
A
A
Thede
C
C
D000327:Adsorption; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D002417:Cattle; D005340:Fibrinogen / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010743:Phospholipids / Q000494:pharmacology; D011510:Proteolipids / Q000037:antagonists & inhibitors*; D011663:Pulmonary Surfactants / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors
D000906:Antibodies; D010743:Phospholipids; D011510:Proteolipids; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D005340:Fibrinogen