SYNDECANS, CELL-SURFACE HEPARAN-SULFATE PROTEOGLYCANS, ARE INDUCED BY A PROLINE-RICH ANTIMICROBIAL PEPTIDE FROM WOUNDS
SYNDECANS, CELL-SURFACE HEPARAN-SULFATE PROTEOGLYCANS, ARE INDUCED BY A PROLINE-RICH ANTIMICROBIAL PEPTIDE FROM WOUNDS
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DOI：
10.1073/pnas.91.23.11035
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发表时间：
1994-11-08
影响因子：
11.1
通讯作者：
BERNFIELD, M
中科院分区：
文献类型：
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作者：
GALLO, RL;ONO, M;BERNFIELD, M
细胞表面硫酸肝素蛋白聚糖，如syndecans，是细胞对肝素结合生长因子和细胞外基质成分的反应所必需的。在小鼠伤口修复过程中，间充质细胞诱导了syndecan-1和4的表达，这与syndecan在这些效应物的作用下调节细胞增殖和迁移的作用一致。在这里，我们发现伤口液具有诱导活性，在外观时间上模仿体内诱导，对间充质细胞的特异性，以及对syndecan-1和-4的选择性。我们从伤口液中纯化并合成了一个4.8 kda的富含脯氨酸的蛋白，该蛋白在培养细胞中复制了syndecan-1和-4的诱导。这种肽与抗菌肽PR-39相同，通过细胞浸润释放到伤口中，并在裂解细菌的相同肽浓度下诱导syndecan表达。这些结果表明，伤口含有一种多功能蛋白，可诱导哺乳动物细胞表达细胞表面硫酸肝素蛋白聚糖，作为伤口修复过程的一部分，并作为非免疫防御机制的一部分杀死细菌。
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 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 effecters. Here we show that wound fluid contains inductive activity that mimics the in vivo induction in time of appearance, specificity 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, identical to the antibacterial peptide PR-39, is released into the wound by the cellular infiltrate 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.