Full length synthetic surfactant proteins, SP-B and SP-C, reduce surfactant inactivation by serum

The failure of some infants with respiratory distress syndrome to respond to therapy with surfactant may be explained in part by inactivation of surfactant caused by leakage of plasma constituents into air spaces. Surfactant-associated proteins (SP-A, SP-B and SP-C) reduce the susceptibility of surfactants to inactivation in vitro. To study this phenomenon further, we used full length synthetic proteins, SP-B [1-78] and SP-C [1-31], mixed with surfactant lipids in different ratios and different concentrations. Equilibrium and minimum surface tensions of these mixtures, with or without serum and calcium, were measured using a pulsating surfactometer. Mixtures containing both SP-B and SP-C had optimal minimum and equilibrium surface tensions of < 5 and < 28 mN/m, respectively. Mixtures with SP-B had optimal minimum surface tensions, but equilibrium surface tensions averaged 35 mN/m. Mixtures with SP-C had high minimal (19 mN/m) and high equilibrium surface tensions (35 mN/m). When serum was added to these mixtures, the least inactivation was found with mixtures containing 3% protein at 1:1 ratio of SP-B/SP-C with 2 mM calcium chloride. These data indicate that SP-B and SP-C, particularly in the presence of calcium, reduce surfactant inactivation that may be caused by plasma constituents. The results lead to the hypothesis that charge interactions among ions, lipids, surfactant proteins, and serum inactivators are a major element in pathophysiological surfactant inactivation.