Characterization of platelet-derived compounds that induce antimicrobial peptides in human keratinocytes

The use of formulations based on thrombocyte concentrate lysates (platelet-released growth factors, PRGF) revealed promising effects in the treatment of chronic wounds. The underlying mechanisms are not well understood. We could show that PRGF induced the expression of antimicrobial peptides (AMPs) such as the human beta-defensin-2 and -3 (hBD-2, hBD-3) in keratinocytes. This may contribute to the observed beneficial effects of PRGF-based formulations in wound treatment. Given that it is unclear which components of platelets induce AMPs in keratinocytes we aimed to biochemically identify PRGF-derived factors that induce hBD-2 and hBD-3 in human keratinocytes. 

Using molecular weight filtration and gel filtration revealed the presence of several proteins between 30-40 kD in hBD-2 and the hBD-3 inducing PRGF fractions. Using sequential two-step RP-HPLC separation we showed that one distinct fraction reproducibly induced hBD-2 and is a candidate fraction for further analysis such as final compound identification. 

These experiments are the basis for the final identification of PRGF-derived mediators that support healing of chronic wounds by their capacity to induce the expression of AMPs in keratinocytes. These mediators could be promising lead substances for the development of drugs that promote would healing and display anti-infective properties via a novel mechanism that induces defensins in human skin. 


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