Processing of Laminin α Chains Generates Peptides Involved in Wound Healing and Host Defense

Autor: Birgit Schittek, Christina Christ, Tilo Biedermann, Martin Schaller, Andreas Maurer, Patricia Rousselle, Luisa Schäfer, Wolfgang Kempf, Gerd Klein, Ines Wanke, Claus Garbe, Stefan Stevanovic, Hubert Kalbacher, Ilknur Senyürek
Rok vydání: 2014
Předmět:
Zdroj: Journal of Innate Immunity. 6:467-484
ISSN: 1662-8128
1662-811X
DOI: 10.1159/000357032
Popis: Laminins play a fundamental role in basement membrane architecture and function in human skin. The C-terminal laminin G domain-like (LG) modules of laminin α chains are modified by proteolysis to generate LG1-3 and secreted LG4-5 tandem modules. In this study, we provide evidence that skin-derived cells process and secrete biologically active peptides from the LG4-5 module of the laminin α3, α4 and α5 chain in vitro and in vivo. We show enhanced expression and processing of the LG4-5 module of laminin α3 in keratinocytes after infection and in chronic wounds in which the level of expression and further processing of the LG4-5 module correlated with the speed of wound healing. Furthermore, bacterial or host-derived proteases promote processing of laminin α3 LG4-5. On a functional level, we show that LG4-5-derived peptides play a role in wound healing. Moreover, we demonstrate that LG4-derived peptides from the α3, α4 and α5 chains have broad antimicrobial activity and possess strong chemotactic activity to mononuclear cells. Thus, the data strongly suggest a novel multifunctional role for laminin LG4-5-derived peptides in human skin and its involvement in physiological processes and pathological conditions such as inflammation, chronic wounds and skin infection.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje