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C-terminal peptides of tissue-factor pathway inhibitor are novel host defense molecules.

Papareddy, Praveen LU ; Kalle, Martina LU ; Kasetty, Gopinath LU ; Mörgelin, Matthias LU ; Rydengård, Victoria LU ; Albiger, Barbara LU ; Lundqvist, Katarina LU ; Malmsten, Martin and Schmidtchen, Artur LU (2010) In Journal of Biological Chemistry 285(36). p.28387-28398
Abstract
Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagulation, but may, via its C-terminus, also modulate cell surface-, heparin-, lipopolysaccharide interactions as well as participate in growth inhibition. Here we show that C-terminal TFPI peptide sequences are antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungi Candida albicans and Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen for the "classical" human antimicrobial peptide LL-37. The... (More)
Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagulation, but may, via its C-terminus, also modulate cell surface-, heparin-, lipopolysaccharide interactions as well as participate in growth inhibition. Here we show that C-terminal TFPI peptide sequences are antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungi Candida albicans and Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen for the "classical" human antimicrobial peptide LL-37. The killing of E. coli, but not P. aeruginosa, by the C-terminal peptide GLIKTKRKRKKQRVKIAYEEIFVKNM, was enhanced in human plasma and largely abolished in heat-inactivated plasma, a phenomenon linked to generation of antimicrobial C3a and activation of the classical pathway of complement activation. Furthermore, GGL27 displayed anti-endotoxic effects in vitro and in vivo in a mouse model of LPS-shock. Importantly, TFPI was found to be expressed in the basal layers of normal epidermis, and was markedly up-regulated in acute skin wounds as well as wound edges of chronic leg ulcers. Furthermore, C-terminal fragments of TFPI were associated with bacteria present in human chronic leg ulcers. These findings suggest a new role for TFPI in cutaneous defense against infections. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
285
issue
36
pages
28387 - 28398
publisher
ASBMB
external identifiers
  • wos:000281404100081
  • pmid:20592020
  • scopus:77956233304
ISSN
1083-351X
DOI
10.1074/jbc.M110.127019
language
English
LU publication?
yes
id
e364c7d0-a692-487d-a95c-985ce45c6bfe (old id 1645421)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20592020?dopt=Abstract
date added to LUP
2010-08-02 10:08:32
date last changed
2018-07-15 03:06:13
@article{e364c7d0-a692-487d-a95c-985ce45c6bfe,
  abstract     = {Tissue factor pathway inhibitor (TFPI) inhibits tissue factor-induced coagulation, but may, via its C-terminus, also modulate cell surface-, heparin-, lipopolysaccharide interactions as well as participate in growth inhibition. Here we show that C-terminal TFPI peptide sequences are antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungi Candida albicans and Candida parapsilosis. Fluorescence studies of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen for the "classical" human antimicrobial peptide LL-37. The killing of E. coli, but not P. aeruginosa, by the C-terminal peptide GLIKTKRKRKKQRVKIAYEEIFVKNM, was enhanced in human plasma and largely abolished in heat-inactivated plasma, a phenomenon linked to generation of antimicrobial C3a and activation of the classical pathway of complement activation. Furthermore, GGL27 displayed anti-endotoxic effects in vitro and in vivo in a mouse model of LPS-shock. Importantly, TFPI was found to be expressed in the basal layers of normal epidermis, and was markedly up-regulated in acute skin wounds as well as wound edges of chronic leg ulcers. Furthermore, C-terminal fragments of TFPI were associated with bacteria present in human chronic leg ulcers. These findings suggest a new role for TFPI in cutaneous defense against infections.},
  author       = {Papareddy, Praveen and Kalle, Martina and Kasetty, Gopinath and Mörgelin, Matthias and Rydengård, Victoria and Albiger, Barbara and Lundqvist, Katarina and Malmsten, Martin and Schmidtchen, Artur},
  issn         = {1083-351X},
  language     = {eng},
  number       = {36},
  pages        = {28387--28398},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {C-terminal peptides of tissue-factor pathway inhibitor are novel host defense molecules.},
  url          = {http://dx.doi.org/10.1074/jbc.M110.127019},
  volume       = {285},
  year         = {2010},
}