Surfactant Protein B Propeptide Contains a Saposin-Like Protein Domain with Antimicrobial Activity at Low pH

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 proprote...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 2010-01, Vol.184 (2), p.975-983
Main Authors: Yang, Li, Johansson, Jan, Ridsdale, Ross, Willander, Hanna, Fitzen, Michael, Akinbi, Henry T, Weaver, Timothy E
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - isolation & purification
Anti-Bacterial Agents - pharmacology
Biochemistry and Molecular Biology
Biokemi och molekylärbiologi
Bronchoalveolar Lavage Fluid - chemistry
Bronchoalveolar Lavage Fluid - immunology
Hydrogen-Ion Concentration
Immunity, Innate
Klebsiella pneumoniae - immunology
Macrophages, Alveolar - microbiology
Medicin och hälsovetenskap
Mice
Mice, Transgenic
Protein Precursors - analysis
Protein Precursors - immunology
Protein Precursors - pharmacology
Protein Structure, Tertiary
Proteolipids - analysis
Proteolipids - immunology
Proteolipids - pharmacology
Saposins
Staphylococcus aureus - immunology
Tissue Distribution
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-1767
1550-6606
1550-6606
DOI:10.4049/jimmunol.0900650