The proteins of the surfactant system

Abstract

The structural and functional integrity of pulmonary surfactant depends on several specific proteins. Two of these, SP-A and SP-D, are large and water- soluble, while SP-B and SP-C are small and very hydrophobic. SP-A is an 18- mer of 26 kDa polypeptide chains and contains N-linked oligosaccharides. Structurally, it can be characterized as a collagen/lectin hybrid. Together with SP-B, SP-A is required for conversion of secreted endogenous surfactant to tubular myelin in the alveolar lining. It also regulates surfactant secretion and reuptake of surfactant lipids by type II cells: these functions are probably receptor mediated. SP-D, a 12-mer of 39 kDa polypeptide chains, is a collagenous glycoprotein with structural similarities to C-type lectins. Both SP-A and SP-D stimulate alveolar macrophages. SP-B is a 79-residue polypeptide that contains three intrachain disulphide bridges. It exists mainly as a homodimer, which is strongly positively charged and may selectively remove anionic and unsaturated lipid species from the alveolar surface film, thereby increasing surface pressure. SP-C is a mainly α- helical, extraordinarily hydrophobic polypeptide containing 35 amino acid residues and covalently linked palmitoyl groups. Its α-helical portion is inserted into surfactant lipid bilayers. SP-C accelerates the adsorption of lipid bilayers to an interfacial monolayer. In babies with respiratory distress syndrome, the clinical response to treatment with surfactant containing SP-B and SP-C is much faster than in babies treated with protein- free synthetic surfactant. We speculate that, in the near future, surfactant preparations based on recombinant hydrophobic proteins will be available for clinical use.