LUNG-FUNCTION IN PREMATURE RABBITS TREATED WITH RECOMBINANT HUMAN SURFACTANT PROTEIN-C

We report the activity of recombinant human surfactant apoprotein-C (r SP-C[Cys](2)) and various phospholipids in a preterm rabbit model of r espiratory distress syndrome (RDS). Mixtures of rSP-C(Cys)(2) and cert ain phospholipids had similar activity (lung compliance and lung press ure-volume behavior) to rabbit surfactant in this model. The activity of rSP-C(Cys)(2) was maximal at 1 mol% protein and varied significantl y with the phospholipid composition. Chemically synthesized SP-C had s imilar activity to rSP-C(Cys)(2). Deletion of six amino-terminal resid ues did not affect function. Substitution of cysteines and cysteines w ith adjacent serines (rSP-C[Ser](2)) by site-specific mutagenesis mini mized aggregation of rSP-C but did not affect activity. Palmitoylation of cysteines and cysteines in rSP-C (rSP-C[C16](2)) did not enhance t he 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.