title: Tissue factor pathway inhibitor 2 is found in skin and its C-terminal region encodes for antibacterial activity.
abstract: 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.
  
  
  RESULTS
  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
  The results demonstrate that the C-terminus of TFPI-2 encodes for antimicrobial activity, and may be released during wounding.
authors.affiliation: Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, Biomedical Center, Lund, Sweden. praveen.papareddy@med.lu.se
authors.forename: Praveen
authors.initials: P
authors.lastname: Papareddy
authors.forename: Martina
authors.initials: M
authors.lastname: Kalle
authors.forename: Ole E
authors.initials: OE
authors.lastname: Sørensen
authors.forename: Katarina
authors.initials: K
authors.lastname: Lundqvist
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.forename: Martin
authors.initials: M
authors.lastname: Malmsten
authors.forename: Artur
authors.initials: A
authors.lastname: Schmidtchen
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D052978:Disk Diffusion Antimicrobial Tests; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D019272:Leukocyte Elastase / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry; D050296:Microbial Viability / Q000187:drug effects; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013211:Staphylococcus aureus / Q000187:drug effects; D046509:Tissue Culture Techniques
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C000591220:EDC34 peptide; D006023:Glycoproteins; D008070:Lipopolysaccharides; D010446:Peptide Fragments; C021240:tissue-factor-pathway inhibitor 2; D019272:Leukocyte Elastase