Leukotriene B4-induced changes in vascular permeability are mediated by neutrophil release of heparin-binding protein (HBP/CAP37/azurocidin)
Leukotriene B4-induced changes in vascular permeability are mediated by neutrophil release of heparin-binding protein (HBP/CAP37/azurocidin)
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DOI：
10.1096/fj.08-121277
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发表时间：
2009-06-01
期刊：
影响因子：
4.8
通讯作者：
Haeggstrom, Jesper Z.
中科院分区：
文献类型：
--
作者：
Di Gennaro, Antonio;Kenne, Ellinor;Haeggstrom, Jesper Z.
在人类中，肝素结合蛋白 (HBP) 和有效的趋化脂质白三烯 B-4 (LTB4) 是先天免疫反应的重要介质。在这里，我们通过蛋白质印迹分析确定，用 LTB4（30 秒至 5 分钟）攻击的人中性粒细胞 (PMN) 会释放 HBP。该反应在 100 nM 激动剂时达到峰值，并由 BLT1 受体介导。蛋白磷酸酶-1 (30 μM) 和渥曼青霉素 (0.5 μM) 阻断 LTB4 介导的 PMN 中 HBP 的释放，这表明脱粒过程中 1-磷脂酰肌醇 3-激酶细胞内途径的参与。此外，LTB4 刺激的 PMN 分泌后上清液在体外诱导内皮细胞内钙动员，并在体内增加血管通透性，正如在小鼠胸膜炎模型中所评估的那样。从上清液中选择性去除 HBP 可显着降低这些活性，这归因于 HBP 在 LTB4 诱导的血管通透性变化中发挥着关键作用。这种脂蛋白轴可以为血管炎症反应关键步骤的药物干预提供新的机会。-Di Gennaro, A.、Kenne, E.、Wan, M.、Soehnlein, O.、Lindbom, L.、Haeggstrom, J. Z. Leukotriene B-4 诱导的血管通透性变化是由中性粒细胞释放肝素结合蛋白 (HBP/CAP37/azurocidin) 介导的。 FASEB J. 23, 1750-1757 (2009)
In humans, heparin-binding protein (HBP) and the potent chemotactic lipid leukotriene B-4 (LTB4) are important mediators of innate immune reponses. Here we show that human neutrophils (PMNs) challenged with LTB4 (30 s to 5 min) release HBP as determined by Western blot analysis. This response peaks at 100 nM of agonist and is mediated by the BLT1 receptor. Protein phosphatase-1 (30 mu M) and wortmannin (0.5 mu M) block the LTB4-mediated HBP release from PMNs, which suggests involvement of the 1-phosphatidylinositol 3-kinase intracellular pathway during degranulation. Furthermore, postsecretory supernatants from LTB4-stimulated PMNs induce intracellular calcium mobilization in endothelial cells in vitro and increase in vascular permeability in vivo, as assessed in a mouse model of pleurisy. Selective removal of HBP from the supernatant significantly reduces these activities attributing a key role to HBP in the LTB4-induced change in vascular permeability. This lipid-protein axis could offer novel opportunities for pharmacological intervention in key steps of the vascular response to inflammation.-Di Gennaro, A., Kenne, E., Wan, M., Soehnlein, O., Lindbom, L., Haeggstrom, J. Z. Leukotriene B-4-induced changes in vascular permeability are mediated by neutrophil release of heparin-binding protein (HBP/CAP37/azurocidin). FASEB J. 23, 1750-1757 (2009)