Lung function in premature rabbits treated with recombinant human surfactant protein-C

We report the activity of recombinant human surfactant apoprotein-C (rSP-C[Cys]2) and various phospholipids in a preterm rabbit model of respiratory distress syndrome (RDS). Mixtures of rSP-C(Cys)2 and certain phospholipids had similar activity (lung compliance and lung pressure-volume behavior) to rabbit surfactant in this model. The activity of rSP-C(Cys)2 was maximal at 1 mol% protein and varied significantly with the phospholipid composition. Chemically synthesized SP-C had similar activity to rSP-C(Cys)2. Deletion of six amino-terminal residues did not affect function. Substitution of cysteines and cysteine6 with adjacent serines (rSP-C[Ser]2) by site-specific mutagenesis minimized aggregation of rSP-C but did not affect activity. Palmitoylation of cysteine5 and cysteine6 in rSP-C (rSP-C[C16]2) did not enhance the activity of rSP-C(Cys)2. We conclude that bacterial expression is a practical source of functional SP-C, and that nonacylated forms of SP-C may be useful adjuvants to phospholipids in the treatment of RDS and possibly other forms of acute lung injury.