title: Aberrant processing of surfactant protein C in hereditary SP-B deficiency.
abstract: Hereditary surfactant protein B (SP-B) deficiency causes lethal neonatal respiratory disease associated with abnormalities in pulmonary surfactant proteins and lipids. SP-C, a 4-kDa hydrophobic protein produced from a 21-kDa precursor, cooperates with SP-B to enhance the surface active properties of surfactant phospholipids. Anti-proSP-C polyclonal antisera were produced against fusion proteins containing 1) the amino terminus (amino acids 1-20), 2) the region carboxy-terminal to the mature SP-C peptide (amino acids 58-77), and 3) full-length 197-amino acid proSP-C and were characterized using immunoprecipitation, Western blot, and immunohistochemical techniques. Western blot analysis of bronchoalveolar lavage and amniotic fluid from hereditary SP-B-deficient patients allowed identification of a 12-kDa form of SP-C that contained epitopes consistent with the amino-terminal and active peptide regions of SP-C (amino acids 1-57). The 12-kDa SP-C peptide was not detected in bronchoalveolar lavage from healthy adults or adults with alveolar proteinosis or pneumonia. We conclude that SP-B deficiency is associated with the aberrant processing and secretion of an immature SP-C peptide, which may contribute to the respiratory failure associated with hereditary SP-B deficiency.
authors.affiliation: Children's Hospital Medical Center, Division of Pulmonary Biology, Cincinnati, Ohio 45229, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Vorbroker
authors.forename: S A
authors.initials: SA
authors.lastname: Profitt
authors.forename: L M
authors.initials: LM
authors.lastname: Nogee
authors.forename: J A
authors.initials: JA
authors.lastname: Whitsett
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D000939:Epitopes; D006801:Humans; D007106:Immune Sera; D007231:Infant, Newborn; D008970:Molecular Weight; D010446:Peptide Fragments / Q000032:analysis; D011498:Protein Precursors / Q000276:immunology; D011499:Protein Processing, Post-Translational; D011510:Proteolipids / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012016:Reference Values
chemical_list: D000939:Epitopes; D007106:Immune Sera; D010446:Peptide Fragments; D011498:Protein Precursors; D011510:Proteolipids; D011663:Pulmonary Surfactants