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Characterization of Released Polypeptides During an Interferon-γ-Dependent Antibacterial Response in Airway Epithelial Cells.

Eliasson, Mette LU ; Olin, Anders LU ; Malmström, Johan; Mörgelin, Matthias LU ; Bodelsson, Mikael LU ; Collin, Mattias LU and Egesten, Arne LU (2012) In Journal of interferon & cytokine research 32(11). p.524-533
Abstract
When pathogenic bacteria breach the epithelial lining at mucosal surfaces, rapidly available innate immune mechanisms are critical to halt the infection. In the present study, we characterized the production of antibacterial polypeptides released by epithelial cells. IFN-γ, but neither TNF nor IL-1β alone, induced release of antibacterial activity to a cell culture medium, causing a lytic appearance of killed bacteria as revealed by electron microscopy. Addition of the protein streptococcal inhibitor of complement, derived from Streptococcus pyogenes, known for its ability to neutralize antimicrobial polypeptides (AMPs), reduced the antibacterial activity of the medium. Characterization of the antibacterial incubation medium using mass... (More)
When pathogenic bacteria breach the epithelial lining at mucosal surfaces, rapidly available innate immune mechanisms are critical to halt the infection. In the present study, we characterized the production of antibacterial polypeptides released by epithelial cells. IFN-γ, but neither TNF nor IL-1β alone, induced release of antibacterial activity to a cell culture medium, causing a lytic appearance of killed bacteria as revealed by electron microscopy. Addition of the protein streptococcal inhibitor of complement, derived from Streptococcus pyogenes, known for its ability to neutralize antimicrobial polypeptides (AMPs), reduced the antibacterial activity of the medium. Characterization of the antibacterial incubation medium using mass spectrometric approaches and ELISAs, displayed presence of several classical AMPs, antibacterial chemokines, as well as complement factors and proteases that may interfere with bacterial killing. Many were constitutively produced, that is, being released by cells incubated in a medium alone. While a combination of IFN-γ and TNF did not increase bacterial killing, the presence of TNF boosted the amounts and detectable number of AMPs, including antibacterial chemokines. However, the methods applied in the study failed to single out certain AMPs as critical mediators, but rather demonstrate the broad range of molecules involved. Since many AMPs are higly amphiphatic in nature (i.e., cationic and hydrophobic), it is possible that difficulties in optimizing recovery present limitations in the context investigated. The findings demonstrate that epithelial cells have a constitutive production of AMPs and that IFN-γ is an important inducer of an antibacterial response in which is likely to be a critical part of the innate host defense against pathogenic bacteria at mucosal surfaces. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of interferon & cytokine research
volume
32
issue
11
pages
524 - 533
publisher
Mary Ann Liebert, Inc.
external identifiers
  • wos:000310842800003
  • pmid:22909116
  • scopus:84869012796
ISSN
1557-7465
DOI
10.1089/jir.2012.0017
language
English
LU publication?
yes
id
740d9257-42e4-4115-b9fe-bd2c22712fec (old id 3047356)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22909116?dopt=Abstract
date added to LUP
2012-09-05 20:16:49
date last changed
2017-01-01 05:39:37
@article{740d9257-42e4-4115-b9fe-bd2c22712fec,
  abstract     = {When pathogenic bacteria breach the epithelial lining at mucosal surfaces, rapidly available innate immune mechanisms are critical to halt the infection. In the present study, we characterized the production of antibacterial polypeptides released by epithelial cells. IFN-γ, but neither TNF nor IL-1β alone, induced release of antibacterial activity to a cell culture medium, causing a lytic appearance of killed bacteria as revealed by electron microscopy. Addition of the protein streptococcal inhibitor of complement, derived from Streptococcus pyogenes, known for its ability to neutralize antimicrobial polypeptides (AMPs), reduced the antibacterial activity of the medium. Characterization of the antibacterial incubation medium using mass spectrometric approaches and ELISAs, displayed presence of several classical AMPs, antibacterial chemokines, as well as complement factors and proteases that may interfere with bacterial killing. Many were constitutively produced, that is, being released by cells incubated in a medium alone. While a combination of IFN-γ and TNF did not increase bacterial killing, the presence of TNF boosted the amounts and detectable number of AMPs, including antibacterial chemokines. However, the methods applied in the study failed to single out certain AMPs as critical mediators, but rather demonstrate the broad range of molecules involved. Since many AMPs are higly amphiphatic in nature (i.e., cationic and hydrophobic), it is possible that difficulties in optimizing recovery present limitations in the context investigated. The findings demonstrate that epithelial cells have a constitutive production of AMPs and that IFN-γ is an important inducer of an antibacterial response in which is likely to be a critical part of the innate host defense against pathogenic bacteria at mucosal surfaces.},
  author       = {Eliasson, Mette and Olin, Anders and Malmström, Johan and Mörgelin, Matthias and Bodelsson, Mikael and Collin, Mattias and Egesten, Arne},
  issn         = {1557-7465},
  language     = {eng},
  number       = {11},
  pages        = {524--533},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Journal of interferon & cytokine research},
  title        = {Characterization of Released Polypeptides During an Interferon-γ-Dependent Antibacterial Response in Airway Epithelial Cells.},
  url          = {http://dx.doi.org/10.1089/jir.2012.0017},
  volume       = {32},
  year         = {2012},
}