Open AccessThe C-Terminal Sequence of Several Human Serine Proteases Encodes Host Defense Functions
Author(s) -
Gopinath Kasetty,
Praveen Papareddy,
Martina Kalle,
Victoria Rydengård,
Björn Walse,
Bo Svensson,
Matthias Mörgelin,
Martin Malmsten,
Artur Schmidtchen
Publication year - 2011
Publication title -
journal of innate immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.078
H-Index - 64
eISSN - 1662-8128
pISSN - 1662-811X
DOI - 10.1159/000327016
Subject(s) - proteases , innate immune system , antimicrobial peptides , serine , kallikrein , biology , serine protease , lipopolysaccharide , biochemistry , microbiology and biotechnology , peptide , protease , immunology , enzyme , receptor
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.