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Coagulation, an ancestral serine protease cascade, exerts a novel function in early immune defense.

Loof, Torsten LU ; Mörgelin, Matthias LU ; Johansson, Linda; Oehmcke, Sonja LU ; Olin, Anders LU ; Dickneite, Gerhard; Norrby-Teglund, Anna; Theopold, Ulrich and Herwald, Heiko LU (2011) In Blood 118. p.2589-2598
Abstract
Phylogenetically conserved serine protease cascades play an important role in invertebrate and vertebrate immunity. The mammalian coagulation system can be traced back some 400 million years and it shares homology with ancestral serine proteinase cascades involved for instance in Toll receptor signaling in insects and release of antimicrobial peptides during hemolymph clotting. Here we show that bacteria-evoked induction of coagulation leads to an immobilization and killing of Streptococcus pyogenes bacteria inside the clot. The entrapment is mediated via crosslinking bacteria to fibrin fibers by the action of coagulation factor XIII (fXIII), an evolutionarily conserved transglutaminase. In a streptococcal skin infection model, fXIII(-/-)... (More)
Phylogenetically conserved serine protease cascades play an important role in invertebrate and vertebrate immunity. The mammalian coagulation system can be traced back some 400 million years and it shares homology with ancestral serine proteinase cascades involved for instance in Toll receptor signaling in insects and release of antimicrobial peptides during hemolymph clotting. Here we show that bacteria-evoked induction of coagulation leads to an immobilization and killing of Streptococcus pyogenes bacteria inside the clot. The entrapment is mediated via crosslinking bacteria to fibrin fibers by the action of coagulation factor XIII (fXIII), an evolutionarily conserved transglutaminase. In a streptococcal skin infection model, fXIII(-/-) mice develop severe signs of pathologic inflammation at the local site of infection and fXIII-treatment of wildtype animals dampens bacterial dissemination during early infection. Bacterial killing and crosslinking to fibrin networks was also detected in tissue biopsies from patients with streptococcal necrotizing fasciitis supporting the concept that coagulation is part of the early innate immune system. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
118
pages
2589 - 2598
publisher
American Society of Hematology
external identifiers
  • wos:000294476400031
  • pmid:21613262
  • scopus:80052397217
ISSN
1528-0020
DOI
10.1182/blood-2011-02-337568
language
English
LU publication?
yes
id
f8e22ca9-48ad-4ac7-8434-a084b191cfab (old id 1972178)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21613262?dopt=Abstract
date added to LUP
2011-06-07 22:29:33
date last changed
2017-11-05 03:26:53
@article{f8e22ca9-48ad-4ac7-8434-a084b191cfab,
  abstract     = {Phylogenetically conserved serine protease cascades play an important role in invertebrate and vertebrate immunity. The mammalian coagulation system can be traced back some 400 million years and it shares homology with ancestral serine proteinase cascades involved for instance in Toll receptor signaling in insects and release of antimicrobial peptides during hemolymph clotting. Here we show that bacteria-evoked induction of coagulation leads to an immobilization and killing of Streptococcus pyogenes bacteria inside the clot. The entrapment is mediated via crosslinking bacteria to fibrin fibers by the action of coagulation factor XIII (fXIII), an evolutionarily conserved transglutaminase. In a streptococcal skin infection model, fXIII(-/-) mice develop severe signs of pathologic inflammation at the local site of infection and fXIII-treatment of wildtype animals dampens bacterial dissemination during early infection. Bacterial killing and crosslinking to fibrin networks was also detected in tissue biopsies from patients with streptococcal necrotizing fasciitis supporting the concept that coagulation is part of the early innate immune system.},
  author       = {Loof, Torsten and Mörgelin, Matthias and Johansson, Linda and Oehmcke, Sonja and Olin, Anders and Dickneite, Gerhard and Norrby-Teglund, Anna and Theopold, Ulrich and Herwald, Heiko},
  issn         = {1528-0020},
  language     = {eng},
  pages        = {2589--2598},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Coagulation, an ancestral serine protease cascade, exerts a novel function in early immune defense.},
  url          = {http://dx.doi.org/10.1182/blood-2011-02-337568},
  volume       = {118},
  year         = {2011},
}