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The Journal of Immunology, 2006, 176: 416-425.
Copyright © 2006 by The American Association of Immunologists

Antimicrobial Activity of Native and Synthetic Surfactant Protein B Peptides1

Marnie A. Ryan*, Henry T. Akinbi*, Alicia G. Serrano{ddagger}, Jesus Perez-Gil{ddagger}, Huixing Wu{dagger}, Francis X. McCormack{dagger} and Timothy E. Weaver2,*

* Division of Pulmonary Biology, Cincinnati Children’s Hospital Medical Center, and University of Cincinnati College of Medicine, and {dagger} Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45229; and {ddagger} Departamento de Bioquimica y Biologia Molecular I, Facultad Biologia, Universidad Complutense, Madrid, Spain

Surfactant protein B (SP-B) is secreted into the airspaces with surfactant phospholipids where it reduces surface tension and prevents alveolar collapse at end expiration. SP-B is a member of the saposin-like family of proteins, several of which have antimicrobial properties. SP-B lyses negatively charged liposomes and was previously reported to inhibit the growth of Escherichia coli in vitro; however, a separate study indicated that elevated levels of SP-B in the airspaces of transgenic mice did not confer resistance to infection. The goal of this study was to assess the antimicrobial properties of native SP-B and synthetic peptides derived from the native peptide. Native SP-B aggregated and killed clinical isolates of Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and group B streptococcus by increasing membrane permeability; however, SP-B also lysed RBC, indicating that the membranolytic activity was not selective for bacteria. Both the antimicrobial and hemolytic activities of native SP-B were inhibited by surfactant phospholipids, suggesting that endogenous SP-B may not play a significant role in alveolar host defense. Synthetic peptides derived from native SP-B were effective at killing both Gram-positive and Gram-negative bacteria at low peptide concentrations (0.15–5.0 µM). The SP-B derivatives selectively lysed bacterial membranes and were more resistant to inhibition by phospholipids; furthermore, helix 1 (residues 7–22) retained significant antimicrobial activity in the presence of native surfactant. These results suggest that the role of endogenous SP-B in host defense may be limited; however, synthetic peptides derived from SP-B may be useful in the treatment of bacterial pneumonias.




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