title: Surfactant protein B propeptide contains a saposin-like protein domain with antimicrobial activity at low pH.
abstract: Surfactant protein B (SP-B) proprotein contains three saposin-like protein (SAPLIP) domains: a SAPLIP domain corresponding to the mature SP-B peptide is essential for lung function and postnatal survival; the function of SAPLIP domains in the N-terminal (SP-BN) and C-terminal regions of the proprotein is not known. In the current study, SP-BN was detected in the supernatant of mouse bronchoalveolar lavage fluid (BALF) and in nonciliated bronchiolar cells, alveolar type II epithelial cells, and alveolar macrophages. rSP-BN indirectly promoted the uptake of bacteria by macrophage cell lines and directly killed bacteria at acidic pH, consistent with a lysosomal, antimicrobial function. Native SP-BN isolated from BALF also killed bacteria but only at acidic pH; the bactericidal activity of BALF at acidic pH was completely blocked by SP-BN Ab. Transgenic mice overexpressing SP-BN and mature SP-B peptide had significantly decreased bacterial burden and increased survival following intranasal inoculation with bacteria. These findings support the hypothesis that SP-BN contributes to innate host defense of the lung by supplementing the nonoxidant antimicrobial defenses of alveolar macrophages.
authors.affiliation: Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Jan
authors.initials: J
authors.lastname: Johansson
authors.forename: Ross
authors.initials: R
authors.lastname: Ridsdale
authors.forename: Hanna
authors.initials: H
authors.lastname: Willander
authors.forename: Michael
authors.initials: M
authors.lastname: Fitzen
authors.forename: Henry T
authors.initials: HT
authors.lastname: Akinbi
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Weaver
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D006863:Hydrogen-Ion Concentration; D007113:Immunity, Innate; D007711:Klebsiella pneumoniae / Q000276:immunology; D016676:Macrophages, Alveolar / Q000382:microbiology; D051379:Mice; D008822:Mice, Transgenic; D011498:Protein Precursors / Q000032:analysis / Q000276:immunology* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011510:Proteolipids / Q000032:analysis / Q000276:immunology* / Q000494:pharmacology; D049231:Saposins; D013211:Staphylococcus aureus / Q000276:immunology; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D011498:Protein Precursors; D011510:Proteolipids; D049231:Saposins; C105511:surfactant protein B propeptide