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

作者：Senyuerek Ilknur; Kempf Wolfgang E; Klein Gerd; Maurer Andreas; Kalbacher Hubert; Schaefer Luisa; Wanke Ines; Christ Christina; Stevanovic Stefan; Schaller Martin; Rousselle Patricia; Garbe Claus; Biedermann Tilo; Schittek Birgit

来源：Journal of Innate Immunity, 2014, 6(4): 467-484.

DOI：10.1159/000357032

• Extracellular matrix
• Laminin
• Antimicrobial peptides.
• Wound healing
• Chemotaxis
• Host defense

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 a 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 a3, a4 and a5 chain in vitro and in vivo. We show enhanced expression and processing of the LG4-5 module of laminin a3 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 a3 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 a3, a4 and a5 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.

• 出版日期2014