Advanced

Proteolysis of human thrombin generates novel host defense peptides.

Papareddy, Praveen LU ; Rydengård, Victoria LU ; Pasupuleti, Mukesh LU ; Walse, Björn; Mörgelin, Matthias LU ; Chalupka, Anna; Malmsten, Martin and Schmidtchen, Artur LU (2010) In PLoS Pathogens 6(4).
Abstract
The coagulation system is characterized by the sequential and highly localized activation of a series of serine proteases, culminating in the conversion of fibrinogen into fibrin, and formation of a fibrin clot. Here we show that C-terminal peptides of thrombin, a key enzyme in the coagulation cascade, constitute a novel class of host defense peptides, released upon proteolysis of thrombin in vitro, and detected in human wounds in vivo. Under physiological conditions, these peptides exert antimicrobial effects against Gram-positive and Gram-negative bacteria, mediated by membrane lysis, as well as immunomodulatory functions, by inhibiting macrophage responses to bacterial lipopolysaccharide. In mice, they are protective against P.... (More)
The coagulation system is characterized by the sequential and highly localized activation of a series of serine proteases, culminating in the conversion of fibrinogen into fibrin, and formation of a fibrin clot. Here we show that C-terminal peptides of thrombin, a key enzyme in the coagulation cascade, constitute a novel class of host defense peptides, released upon proteolysis of thrombin in vitro, and detected in human wounds in vivo. Under physiological conditions, these peptides exert antimicrobial effects against Gram-positive and Gram-negative bacteria, mediated by membrane lysis, as well as immunomodulatory functions, by inhibiting macrophage responses to bacterial lipopolysaccharide. In mice, they are protective against P. aeruginosa sepsis, as well as lipopolysaccharide-induced shock. Moreover, the thrombin-derived peptides exhibit helical structures upon binding to lipopolysaccharide and can also permeabilize liposomes, features typical of "classical" helical antimicrobial peptides. These findings provide a novel link between the coagulation system and host-defense peptides, two fundamental biological systems activated in response to injury and microbial invasion. (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
PLoS Pathogens
volume
6
issue
4
publisher
Public Library of Science
external identifiers
  • wos:000277722400029
  • pmid:20421939
  • scopus:85020592493
ISSN
1553-7366
DOI
10.1371/journal.ppat.1000857
language
English
LU publication?
yes
id
37b4af9a-c619-4afc-997b-a10401a2a764 (old id 1594763)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20421939?dopt=Abstract
date added to LUP
2010-05-04 22:49:31
date last changed
2018-06-24 04:46:03
@article{37b4af9a-c619-4afc-997b-a10401a2a764,
  abstract     = {The coagulation system is characterized by the sequential and highly localized activation of a series of serine proteases, culminating in the conversion of fibrinogen into fibrin, and formation of a fibrin clot. Here we show that C-terminal peptides of thrombin, a key enzyme in the coagulation cascade, constitute a novel class of host defense peptides, released upon proteolysis of thrombin in vitro, and detected in human wounds in vivo. Under physiological conditions, these peptides exert antimicrobial effects against Gram-positive and Gram-negative bacteria, mediated by membrane lysis, as well as immunomodulatory functions, by inhibiting macrophage responses to bacterial lipopolysaccharide. In mice, they are protective against P. aeruginosa sepsis, as well as lipopolysaccharide-induced shock. Moreover, the thrombin-derived peptides exhibit helical structures upon binding to lipopolysaccharide and can also permeabilize liposomes, features typical of "classical" helical antimicrobial peptides. These findings provide a novel link between the coagulation system and host-defense peptides, two fundamental biological systems activated in response to injury and microbial invasion.},
  articleno    = {e1000857},
  author       = {Papareddy, Praveen and Rydengård, Victoria and Pasupuleti, Mukesh and Walse, Björn and Mörgelin, Matthias and Chalupka, Anna and Malmsten, Martin and Schmidtchen, Artur},
  issn         = {1553-7366},
  language     = {eng},
  number       = {4},
  publisher    = {Public Library of Science},
  series       = {PLoS Pathogens},
  title        = {Proteolysis of human thrombin generates novel host defense peptides.},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1000857},
  volume       = {6},
  year         = {2010},
}