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 resp ond to therapy with surfactant may be explained in part by inactivatio n of surfactant caused by leakage of plasma constituents into air spac es. Surfactant-associated proteins (SP-A, SP-B and SP-C) reduce the su sceptibility of surfactants to inactivation in vitro. To study this ph enomenon 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 tension s, but equilibrium surface tensions averaged 35 mN/m. Mixtures with SP -C had high minimal (19 mN/m) and high equilibrium surface tensions (3 5 mN/m). When serum was added to these mixtures, the least inactivatio n was found with mixtures containing 3% protein at 1:1 ratio of SP-B/S P-C with 2 mM calcium chloride. These data indicate that SP-B and SP-C , particularly in the presence of calcium, reduce surfactant inactivat ion that may be caused by plasma constituents. The results lead to the hypothesis that charge interactions among ions, lipids, surfactant pr oteins, and serum inactivators are a major element in pathophysiologic al surfactant inactivation.