Syndecans, cell surface heparan sulfate proteoglycans, are induced by a proline-rich antimicrobial peptide from wounds.

Abstract

Cell surface heparan sulfate proteoglycans, such as the syndecans, are required for cellular responses to heparin-binding growth factors and extraceflular matrix components. Expression of syndecan-1 and -4 is induced in mesenchymal cells during wound repair in the mouse, consistent with a role for syndecans in regulating cell proliferation and migration in response to these effectors. Here we show that wound fluid contains inductive activity that mimics the in vivo induction in time of appearance, specifcity for mesenchymal cells, and selectivity for syndecan-1 and -4. We have purified and synthesized a 4.8-kDa proline-rich protein from wound fluid that reproduces this induction of syndecan-1 and -4 in cultured cells. This peptide, identicai to the antibacterial peptide PR-39, is released into the wound by the cellular infirate and induces syndecan expression at the same peptide concentrations that lyse bacteria. These results indicate that wounds contain a multifunctional 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.

Syndecans: multifunctional cell-surface co-receptors

“…In endothelial cells syndecan-1 expression is subject to negative regulation by tumour necrosis factor-α [53]. Syndecan-1 and syndecan-4 expression by mesenchymal cells at sites of cutaneous wound healing has been shown to be induced by an antimicrobial peptide, PR-39, that is released by inflammatory cells entering the skin [54]. Induction of syndecan expression by PR-39 is selective for mesenchymal cells, and is not detected in epithelial cells or keratinocytes.…”

Cathelicidins: a novel protein family with a common proregion and a variable C‐terminal antimicrobial domain

“…Rabbit and human CAP18 bind LPS, inhibit multiple LPS biological activities in vitro, and reduce LPS lethality in murine models of endotoxemia [33,53], whereas PR-39 can induce expression of cell surface heparan sulphate proteoglycans (syndecan-1 and -4), as part of the wound repair process [54]. These molecules thus appear to be capable of performing several functions, such as bacterial killing, LPSneutralization, inhibition of a tissue-degrading enzyme and promotion of wound healing, which in general are related to the protection of the host.…”

Cathelicidins in inflammation and tissue repair: Potential therapeutic applications for gastrointestinal disorders

“…The ability of cathelicidin to induce angiogenesis further highlights its potential role in wound repair [37] . The pro-healing effects of cathelicidin may be mediated through modification of growth-factor/receptor interactions and angiogenesis [38][39][40] . Definitive proof of the involvement of these mechanisms in wound healing, however, has not yet been obtained.…”