C-terminal peptides of tissue-factor pathway inhibitor are novel host defense molecules.
(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:
https://lup.lub.lu.se/record/1645421
- author
- Papareddy, Praveen LU ; Kalle, Martina LU ; Kasetty, Gopinath LU ; Mörgelin, Matthias LU ; Rydengård, Victoria LU ; Albiger, Barbara LU ; Lundqvist, Katarina LU ; Malmsten, Martin LU and Schmidtchen, Artur LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 285
- issue
- 36
- pages
- 28387 - 28398
- publisher
- American Society for Biochemistry and Molecular Biology
- 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
- 2016-04-01 10:06:52
- date last changed
- 2022-02-02 06:34:06
@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 = {{American Society for Biochemistry and Molecular Biology}}, 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}}, doi = {{10.1074/jbc.M110.127019}}, volume = {{285}}, year = {{2010}}, }