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.