Journal article
SPLUNC1/BPIFA1 Contributes to Pulmonary Host Defense against Klebsiella pneumoniae Respiratory Infection
The American journal of pathology, Vol.182(5), pp.1519-1531
05/2013
DOI: 10.1016/j.ajpath.2013.01.050
PMCID: PMC3644735
PMID: 23499554
Abstract
Epithelial host defense proteins comprise a critical component of the pulmonary innate immune response to infection. The short palate, lung, nasal epithelium clone (PLUNC) 1 (SPLUNC1) protein is a member of the bactericidal/permeability-increasing (BPI) fold-containing (BPIF) protein family, sharing structural similarities with BPI-like proteins. SPLUNC1 is a 25 kDa secretory protein that is expressed in nasal, oropharyngeal, and lung epithelia, and has been implicated in airway host defense against
Pseudomonas aeruginosa
and other organisms. SPLUNC1 is reported to have surfactant properties, which may contribute to anti-biofilm defenses. The objective of this study was to assess the importance of SPLUNC1 surfactant activity in airway epithelial secretions and to explore its biological relevance in the context of a bacterial infection model. Using cultured airway epithelia, we confirmed that SPLUNC1 is critically important for maintenance of low surface tension in airway fluids. Furthermore, we demonstrated that recombinant SPLUNC1 (rSPLUNC1) significantly inhibited
Klebsiella pneumoniae
biofilm formation on airway epithelia. We subsequently found that
Splunc1
−/−
mice were significantly more susceptible to infection with
K. pneumoniae
, confirming the likely
in vivo
relevance of this anti-biofilm effect. Our data indicate that SPLUNC1 is a crucial component of mucosal innate immune defense against pulmonary infection by a relevant airway pathogen, and provide further support for the novel hypothesis that SPLUNC1 protein prevents bacterial biofilm formation through its ability to modulate surface tension of airway fluids.
Details
- Title: Subtitle
- SPLUNC1/BPIFA1 Contributes to Pulmonary Host Defense against Klebsiella pneumoniae Respiratory Infection
- Creators
- Yang Liu - Department of Environmental and Occupational Health, University of Pittsburgh, PennsylvaniaJennifer A Bartlett - Department of Pediatrics, University of Iowa, Iowa City, IowaMarissa E Di - Department of Environmental and Occupational Health, University of Pittsburgh, PennsylvaniaJennifer M Bomberger - Department of Microbiology and Molecular Genetics, University of Pittsburgh, PennsylvaniaYvonne R Chan - Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, PennsylvaniaLokesh Gakhar - Department of Biochemistry and Protein Crystallography Facility, University of Iowa, Iowa City, IowaRama K Mallampalli - Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, PennsylvaniaPaul B McCray - Department of Pediatrics, University of Iowa, Iowa City, IowaY. Peter Di - Department of Environmental and Occupational Health, University of Pittsburgh, Pennsylvania
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.182(5), pp.1519-1531
- Publisher
- American Society for Investigative Pathology
- DOI
- 10.1016/j.ajpath.2013.01.050
- PMID
- 23499554
- PMCID
- PMC3644735
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Language
- English
- Date published
- 05/2013
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Biochemistry and Molecular Biology; Medicine Administration; Internal Medicine
- Record Identifier
- 9984093215902771
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