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The C-Terminal Sequence of Several Human Serine Proteases Encodes Host Defense Functions.

Kasetty, Gopinath LU ; Papareddy, Praveen LU ; Kalle, Martina LU ; Rydengård, Victoria LU ; Walse, Björn; Svensson, Bo; Mörgelin, Matthias LU ; Malmsten, Martin and Schmidtchen, Artur LU (2011) In Journal of Innate Immunity 3(5). p.471-482
Abstract
Serine proteases of the S1 family have maintained a common structure over an evolutionary span of more than one billion years, and evolved a variety of substrate specificities and diverse biological roles, involving digestion and degradation, blood clotting, fibrinolysis and epithelial homeostasis. We here show that a wide range of C-terminal peptide sequences of serine proteases, particularly from the coagulation and kallikrein systems, share characteristics common with classical antimicrobial peptides of innate immunity. Under physiological conditions, these peptides exert antimicrobial effects as well as immunomodulatory functions by inhibiting macrophage responses to bacterial lipopolysaccharide. In mice, selected peptides are... (More)
Serine proteases of the S1 family have maintained a common structure over an evolutionary span of more than one billion years, and evolved a variety of substrate specificities and diverse biological roles, involving digestion and degradation, blood clotting, fibrinolysis and epithelial homeostasis. We here show that a wide range of C-terminal peptide sequences of serine proteases, particularly from the coagulation and kallikrein systems, share characteristics common with classical antimicrobial peptides of innate immunity. Under physiological conditions, these peptides exert antimicrobial effects as well as immunomodulatory functions by inhibiting macrophage responses to bacterial lipopolysaccharide. In mice, selected peptides are protective against lipopolysaccharide-induced shock. Moreover, these S1-derived host defense peptides exhibit helical structures upon binding to lipopolysaccharide and also permeabilize liposomes. The results uncover new and fundamental aspects on host defense functions of serine proteases present particularly in blood and epithelia, and provide tools for the identification of host defense molecules of therapeutic interest. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Proteinase, Endotoxin, Host defense, Antimicrobial peptide, Coagulation
in
Journal of Innate Immunity
volume
3
issue
5
pages
471 - 482
publisher
Karger
external identifiers
  • wos:000294572500005
  • pmid:21576923
  • scopus:80052048215
ISSN
1662-811X
DOI
10.1159/000327016
language
English
LU publication?
yes
id
2b4996be-bd5a-4c6e-84d0-ec0f297d662f (old id 1972484)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21576923?dopt=Abstract
date added to LUP
2011-06-07 21:02:07
date last changed
2017-08-06 03:19:09
@article{2b4996be-bd5a-4c6e-84d0-ec0f297d662f,
  abstract     = {Serine proteases of the S1 family have maintained a common structure over an evolutionary span of more than one billion years, and evolved a variety of substrate specificities and diverse biological roles, involving digestion and degradation, blood clotting, fibrinolysis and epithelial homeostasis. We here show that a wide range of C-terminal peptide sequences of serine proteases, particularly from the coagulation and kallikrein systems, share characteristics common with classical antimicrobial peptides of innate immunity. Under physiological conditions, these peptides exert antimicrobial effects as well as immunomodulatory functions by inhibiting macrophage responses to bacterial lipopolysaccharide. In mice, selected peptides are protective against lipopolysaccharide-induced shock. Moreover, these S1-derived host defense peptides exhibit helical structures upon binding to lipopolysaccharide and also permeabilize liposomes. The results uncover new and fundamental aspects on host defense functions of serine proteases present particularly in blood and epithelia, and provide tools for the identification of host defense molecules of therapeutic interest.},
  author       = {Kasetty, Gopinath and Papareddy, Praveen and Kalle, Martina and Rydengård, Victoria and Walse, Björn and Svensson, Bo and Mörgelin, Matthias and Malmsten, Martin and Schmidtchen, Artur},
  issn         = {1662-811X},
  keyword      = {Proteinase,Endotoxin,Host defense,Antimicrobial peptide,Coagulation},
  language     = {eng},
  number       = {5},
  pages        = {471--482},
  publisher    = {Karger},
  series       = {Journal of Innate Immunity},
  title        = {The C-Terminal Sequence of Several Human Serine Proteases Encodes Host Defense Functions.},
  url          = {http://dx.doi.org/10.1159/000327016},
  volume       = {3},
  year         = {2011},
}