Role of processed peptides of the basement membrane component laminin in skin barrier function

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Laminins play a fundamental role in basement membrane architecture and function in human skin. The C-terminal LG modules of several laminin ý chains can be modified by proteolysis generating a LG1-3 and secreted LG4-5 module. Our preliminary data show that synthetic peptides derived from laminin ý3, ý4 and ý5 chain LG4 modules have effective antimicrobial activity and are able to kill bacteria by membrane permeabilization. In addition, LG4-derived peptides promote migration/proliferation of keratinocytes and have chemotactic activity for monocytes. Interestingly, expression of laminin can be increased after bacterial infection. Based on these data, we propose that secreted laminin LG4-5-derived peptides provide a basal level of protection in skin under physiological conditions and that after tissue damage/skin wounding and/or bacterial infection laminin expression and secretion is induced as well as protease activity which results in increased levels of processed LG4-5 peptides. In the proposal we will identify the naturally processed laminin LG4-5 peptides under normal physiological and infectious conditions in human skin as well as in wounded skin and explore the functional role of the LG4-5 derived processed peptides in skin innate defense. The data should indicate whether processed peptides from the laminin LG4-5 modules play an important role in skin barrier function protecting human skin against infection.