Jiang, D and Wenzel, SE and Wu, Q and Bowler, RP and Schnell, C and Chu, HW
(2013)
Human Neutrophil Elastase Degrades SPLUNC1 and Impairs Airway Epithelial Defense against Bacteria.
PLoS ONE, 8 (5).
Abstract
Background:Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a significant cause of mortality of COPD patients, and pose a huge burden on healthcare. One of the major causes of AECOPD is airway bacterial (e.g. nontypeable Haemophilus influenzae [NTHi]) infection. However, the mechanisms underlying bacterial infections during AECOPD remain poorly understood. As neutrophilic inflammation including increased release of human neutrophil elastase (HNE) is a salient feature of AECOPD, we hypothesized that HNE impairs airway epithelial defense against NTHi by degrading airway epithelial host defense proteins such as short palate, lung, and nasal epithelium clone 1 (SPLUNC1).Methodology/Main Results:Recombinant human SPLUNC1 protein was incubated with HNE to confirm SPLUNC1 degradation by HNE. To determine if HNE-mediated impairment of host defense against NTHi was SPLUNC1-dependent, SPLUNC1 protein was added to HNE-treated primary normal human airway epithelial cells. The in vivo function of SPLUNC1 in NTHi defense was investigated by infecting SPLUNC1 knockout and wild-type mice intranasally with NTHi. We found that: (1) HNE directly increased NTHi load in human airway epithelial cells; (2) HNE degraded human SPLUNC1 protein; (3) Recombinant SPLUNC1 protein reduced NTHi levels in HNE-treated human airway epithelial cells; (4) NTHi levels in lungs of SPLUNC1 knockout mice were increased compared to wild-type mice; and (5) SPLUNC1 was reduced in lungs of COPD patients.Conclusions:Our findings suggest that SPLUNC1 degradation by neutrophil elastase may increase airway susceptibility to bacterial infections. SPLUNC1 therapy likely attenuates bacterial infections during AECOPD. © 2013 Jiang et al.
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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID ![](/images/orcid_id_24x24.png) |
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Jiang, D | | | | Wenzel, SE | | | | Wu, Q | | | | Bowler, RP | | | | Schnell, C | | | | Chu, HW | | | |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID ![](/images/orcid_id_24x24.png) |
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Editor | Jeyaseelan, Samithamby | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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Date: |
31 May 2013 |
Date Type: |
Publication |
Journal or Publication Title: |
PLoS ONE |
Volume: |
8 |
Number: |
5 |
DOI or Unique Handle: |
10.1371/journal.pone.0064689 |
Schools and Programs: |
School of Medicine > Pathology |
Refereed: |
Yes |
Date Deposited: |
15 Jul 2013 20:18 |
Last Modified: |
02 Feb 2019 14:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/19203 |
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