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Syntltetic peptides based on the native human sequen¢~ of surfactant protein B have I~,en used to generate polyclonal monospecific antibodies against specific segments of the native SP-B protein, Circular dichroism analysis or the synthr.tic p, have a dominant helical content in structure promotinll environments and tensiometric measurements indicate these peptides lower surface tension at air=water interfaces implyin~ that they contain amphipathic alpha helical motifs, Antibodies directed aBainst the C-terminal segment of SP.B react with the native protein in the oxidized and reduced state, Antibodies directed against the N.tem~inal sequence of SP-B react with the native protein only in the reduced stat~ suue..aiai| that this domain has a conformation dependent on disulfide bond formation.Surfactant pcptide; Amphtpathie helix: lmmunodominance

Although surfactant replacement therapy has dramatically improved the outcome of premature infants with respiratory distress syndrome, approximately 30% of treated infants show a transient or no response. Nonresponse to surfactant replacement therapy may be due to extreme lung immaturity and possibly surfactant inactivation. Surfactant inactivation involves aspecific biophysical events, such as interference with the formation or activity of an alveolar monolayer, and specific interactions with serum proteins, including antibodies, leaking into the alveolar space. As formulations containing surfactant proteins appear to better tolerate serum inactivation, we used an excised rat lung model to compare the susceptibility to serum inactivation of a mixture of synthetic phospholipids selected from surfactant lipid constituents, Exosurf (a protein-free synthetic surfactant), Survanta [containing surfactant proteins B and C (SP-B and -C)], and a porcine surfactant (containing SP-A, -B, and -C). For each of these preparations, we used pressure/volume determinations as an in situ measure of surfactant activity and retested the same preparations after mixing with human serum, a nonspecific surfactant inactivator. Human serum inactivated porcine surfactant to a lesser extent than Survanta, Exosurf, or synthetic phospholipids. Temperature exerted a significant effect on deflation stability, as shown by a greater lung compliance in untreated, normal lungs and a larger improvement in compliance after treating lavaged lungs with synthetic phospholipids at 37 degrees C than at 22 degrees C. We conclude that surfactant containing SP-A, -B, and -C is only moderately susceptible to inactivation with whole serum and may therefore exert a greater clinical response than protein-free surfactants or those containing only SP-B and -C.

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