Processing of laminin α chains generates peptides involved in wound healing and host defense

J Innate Immun. 2014;6(4):467-84. doi: 10.1159/000357032. Epub 2014 Jan 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / metabolism*
  • Bacterial Infections / immunology*
  • Candidiasis / immunology*
  • Cell Line, Transformed
  • Cell Survival
  • Chemotaxis
  • Humans
  • Immunity, Innate
  • Keratinocytes / microbiology
  • Keratinocytes / physiology*
  • Laminin / genetics
  • Laminin / metabolism*
  • Leukocytes, Mononuclear / physiology*
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • Proteolysis
  • Skin / immunology
  • Skin / microbiology
  • Skin / pathology*
  • Wound Healing


  • Anti-Infective Agents
  • Laminin
  • Peptide Fragments
  • laminin A