Proteolysis of human thrombin generates novel host defense peptides.
(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:
https://lup.lub.lu.se/record/1594763
- author
- Papareddy, Praveen LU ; Rydengård, Victoria LU ; Pasupuleti, Mukesh LU ; Walse, Björn ; Mörgelin, Matthias LU ; Chalupka, Anna ; Malmsten, Martin LU and Schmidtchen, Artur LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS Pathogens
- volume
- 6
- issue
- 4
- article number
- e1000857
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000277722400029
- pmid:20421939
- 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
- 2016-04-04 07:13:38
- date last changed
- 2022-02-13 04:44:33
@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.}}, 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 (PLoS)}}, series = {{PLoS Pathogens}}, title = {{Proteolysis of human thrombin generates novel host defense peptides.}}, url = {{https://lup.lub.lu.se/search/files/5131306/1615888.pdf}}, doi = {{10.1371/journal.ppat.1000857}}, volume = {{6}}, year = {{2010}}, }