The Structure and Function of Surfactant Protein-A

Abstract

The interface between the lung and the atmosphere poses major challenges for all air-breathing organisms. The pulmonary alveolus, the gas-exchanging unit of the lung, is a delicate structure that is prone to collapse under the influence of natural intermolecular forces at the air-tissue boundary. 1 Pattle RE Properties, function and origin of the alveolar lining layer.. Nature. 1955; 175: 1125-1126 Crossref PubMed Scopus (396) Google Scholar The patency of the airspaces is maintained by an oily substance called pulmonary surfactant, which reduces surface tension within the aqueous lining layer that blankets the pulmonary epithelium. 2 Clements JA Hustead RF Johnson RP et al. Pulmonary surface tension and alveolar stability.. J Appl Physiol. 1961; 16: 444-450 PubMed Google Scholar Surfactant is composed of both phospholipids and proteins, 3 King RJ Clements JA Surface active materials from dog: I. Method of isolation.. Am J Physiol. 1972; 223: 707-714 PubMed Google Scholar but most of the surface activity is attributable to the major phospholipid component, dipalmitoylphosphatidylcholine (DPPC). Surfactant phospholipids assemble at the air-liquid interface into a tightly packed, noncompressible monomolecular membrane with a very low surface pressure. 2 Clements JA Hustead RF Johnson RP et al. Pulmonary surface tension and alveolar stability.. J Appl Physiol. 1961; 16: 444-450 PubMed Google Scholar The three surfactant proteins that are unique to the lung and intimately associated with surfactant lipids are surfactant proteins A, 4 King RJ The surfactant system of the lung.. Fed Proc. 1974; 33: 2238-2247 PubMed Google Scholar B, 5 Jacobs KA Phelps DS Steinbrink R et al. Isolation of a cDNA clone encoding a high molecular weight precursor to a 6 kDa pulmonary surfactant associated protein.. J Biol Chem. 1987; 262: 9808-9811 PubMed Google Scholar , 6 Hawgood S Benson BJ Schilling J et al. Nucleotide and amino acid sequences of pulmonary surfactant protein SP 18 and evidence for cooperation between SP 18 and SP 28–36 in surfactant lipid adsorption.. Proc Natl Acad Sci USA. 1987; 84: 66-70 Crossref PubMed Scopus (312) Google Scholar , 7 Glasser SW Korfhagen TR Weaver TE et al. cDNA and deduced amino acid sequence of human pulmonary surfactant-associated proteolipid SPL(Phe).. Proc Natl Acad Sci USA. 1987; 84: 4007-4011 Crossref PubMed Scopus (128) Google Scholar and C 8 Glasser SW Korfhagen TR Weaver TE et al. cDNA, deduced polypeptide structure and chromosomal assignment of human pulmonary surfactant proteolipid SP-C (pVal).. J Biol Chem. 1988; 263: 9-12 PubMed Google Scholar , 9 Warr RG Hawgood SH Buckley TM et al. Low molecular weight human pulmonary surfactant protein (SP5): isolation, characterization, and cDNA sequence.. Proc Natl Acad Sci USA. 1987; 84: 7915-7919 Crossref PubMed Scopus (151) Google Scholar (SP-A, SP-B, SP-C, respectively). As a group, the surfactant proteins function in the delivery of surfactant phospholipids to the monolayer, the spreading of phospholipids at the interface, and the structure of surfactant aggregates (for review see Weaver and Whitsett 10 Weaver TE Whitsett JA Function and regulation of expression of pulmonary surfactant-associated proteins.. Biochem J. 1991; 273: 249-264 Crossref PubMed Scopus (356) Google Scholar ). A more recently described polypeptide in the alveolar space, SP-D, 11 Persson A Chang D Rust K et al. Purification and biochemical characterization of CP4 (SP-D), a collagenous surfactant-associated protein.. Biochemistry. 1989; 28: 6361-6367 Crossref PubMed Scopus (147) Google Scholar has no clear role in the surface active functions of surfactant and is probably a host defense protein. 12 Kuan S Rust K Crouch E Interactions of surfactant protein D with bacterial lipopolysaccharides.. J Clin Invest. 1992; 90: 97-106 Crossref PubMed Scopus (275) Google Scholar