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Tissue Factor Pathway Inhibitor 2 Is Found in Skin and Its C-Terminal Region Encodes for Antibacterial Activity

BACKGROUND: Tissue factor pathway inhibitor 2 (TFPI-2) is a matrix-associated serine protease inhibitor with an enigmatic function in vivo. Here, we describe that TFPI-2 is present in fibrin of wounds and also expressed in skin, where it is up-regulated upon wounding. METHODOLOGY AND PRINCIPAL FINDI...

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Autores principales: Papareddy, Praveen, Kalle, Martina, Sørensen, Ole E., Lundqvist, Katarina, Mörgelin, Matthias, Malmsten, Martin, Schmidtchen, Artur
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530512/
https://www.ncbi.nlm.nih.gov/pubmed/23300768
http://dx.doi.org/10.1371/journal.pone.0052772
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author Papareddy, Praveen
Kalle, Martina
Sørensen, Ole E.
Lundqvist, Katarina
Mörgelin, Matthias
Malmsten, Martin
Schmidtchen, Artur
author_facet Papareddy, Praveen
Kalle, Martina
Sørensen, Ole E.
Lundqvist, Katarina
Mörgelin, Matthias
Malmsten, Martin
Schmidtchen, Artur
author_sort Papareddy, Praveen
collection PubMed
description BACKGROUND: Tissue factor pathway inhibitor 2 (TFPI-2) is a matrix-associated serine protease inhibitor with an enigmatic function in vivo. Here, we describe that TFPI-2 is present in fibrin of wounds and also expressed in skin, where it is up-regulated upon wounding. METHODOLOGY AND PRINCIPAL FINDINGS: Neutrophil elastase cleaved TFPI-2, and a C-terminal fragment was found to bind to bacteria. Similarly, a prototypic peptide representing this C-terminal part, EDC34, bound to bacteria and bacterial lipopolysaccharide, and induced bacterial permeabilization. The peptide also induced leakage in artificial liposomes, and displayed a random coil conformation upon interactions with liposomes as well as lipopolysaccharide. EDC34 was antibacterial against both Gram-negative and Gram-positive bacteria in physiological buffer conditions. CONCLUSIONS/SIGNIFICANCE: The results demonstrate that the C-terminus of TFPI-2 encodes for antimicrobial activity, and may be released during wounding.
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spelling pubmed-35305122013-01-08 Tissue Factor Pathway Inhibitor 2 Is Found in Skin and Its C-Terminal Region Encodes for Antibacterial Activity Papareddy, Praveen Kalle, Martina Sørensen, Ole E. Lundqvist, Katarina Mörgelin, Matthias Malmsten, Martin Schmidtchen, Artur PLoS One Research Article BACKGROUND: Tissue factor pathway inhibitor 2 (TFPI-2) is a matrix-associated serine protease inhibitor with an enigmatic function in vivo. Here, we describe that TFPI-2 is present in fibrin of wounds and also expressed in skin, where it is up-regulated upon wounding. METHODOLOGY AND PRINCIPAL FINDINGS: Neutrophil elastase cleaved TFPI-2, and a C-terminal fragment was found to bind to bacteria. Similarly, a prototypic peptide representing this C-terminal part, EDC34, bound to bacteria and bacterial lipopolysaccharide, and induced bacterial permeabilization. The peptide also induced leakage in artificial liposomes, and displayed a random coil conformation upon interactions with liposomes as well as lipopolysaccharide. EDC34 was antibacterial against both Gram-negative and Gram-positive bacteria in physiological buffer conditions. CONCLUSIONS/SIGNIFICANCE: The results demonstrate that the C-terminus of TFPI-2 encodes for antimicrobial activity, and may be released during wounding. Public Library of Science 2012-12-26 /pmc/articles/PMC3530512/ /pubmed/23300768 http://dx.doi.org/10.1371/journal.pone.0052772 Text en © 2012 Papareddy et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Papareddy, Praveen
Kalle, Martina
Sørensen, Ole E.
Lundqvist, Katarina
Mörgelin, Matthias
Malmsten, Martin
Schmidtchen, Artur
Tissue Factor Pathway Inhibitor 2 Is Found in Skin and Its C-Terminal Region Encodes for Antibacterial Activity
title Tissue Factor Pathway Inhibitor 2 Is Found in Skin and Its C-Terminal Region Encodes for Antibacterial Activity
title_full Tissue Factor Pathway Inhibitor 2 Is Found in Skin and Its C-Terminal Region Encodes for Antibacterial Activity
title_fullStr Tissue Factor Pathway Inhibitor 2 Is Found in Skin and Its C-Terminal Region Encodes for Antibacterial Activity
title_full_unstemmed Tissue Factor Pathway Inhibitor 2 Is Found in Skin and Its C-Terminal Region Encodes for Antibacterial Activity
title_short Tissue Factor Pathway Inhibitor 2 Is Found in Skin and Its C-Terminal Region Encodes for Antibacterial Activity
title_sort tissue factor pathway inhibitor 2 is found in skin and its c-terminal region encodes for antibacterial activity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530512/
https://www.ncbi.nlm.nih.gov/pubmed/23300768
http://dx.doi.org/10.1371/journal.pone.0052772
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