SYNDECANS, CELL-SURFACE HEPARAN-SULFATE PROTEOGLYCANS, ARE INDUCED BYA PROLINE-RICH ANTIMICROBIAL PEPTIDE FROM WOUNDS

Cell surface heparan sulfate proteoglycans, such as the syndecans, are required for cellular responses to heparin-binding growth factors and extracellular matrix components. Expression of syndecan-1 and 4 is in duced in mesenchymal cells during wound repair in the mouse, consisten t with a role for syndecans in regulating cell proliferation and migra tion in response to these effecters. Here we show that wound fluid con tains inductive activity that mimics the in vivo induction in time of appearance, specificity for mesenchymal cells, and selectivity for syn decan-1 and -4. We have purified and synthesized a 4.8-kDa proline-ric h protein from wound fluid that reproduces this induction of syndecan- 1 and -4 in cultured cells. This peptide, identical to the antibacteri al peptide PR-39, is released into the wound by the cellular infiltrat e and induces syndecan expression at the same peptide concentrations t hat lyse bacteria. These results indicate that wounds contain a multif unctional protein that induces mammalian cells to express cell surface heparan sulfate proteoglycans as part of the wound repair process and that kills bacteria as part of a nonimmune defense mechanism.