• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >Endocytic pathway for surfactant protein A in human macrophages: binding, clathrin-mediated uptake, and trafficking through the endolysosomal pathway.
【24h】

Endocytic pathway for surfactant protein A in human macrophages: binding, clathrin-mediated uptake, and trafficking through the endolysosomal pathway.

机译：人巨噬细胞中表面活性剂蛋白A的内吞途径：结合，网格蛋白介导的摄取和通过内溶酶体途径的运输。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

In the noninflamed lung, surfactant protein A (SP-A) acts as an anti-inflammatory molecule through its effects on macrophage (MPhi) function, modulating cytokine and reactive oxygen and nitrogen intermediate production. The receptors responsible for these effects of SP-A on human MPhi are not clear, although SP-A binding to several proteins has been described. In this study, we demonstrate high-affinity specific binding of SP-A to primary human MPhi. SP-A binding was inhibited by EGTA, indicating calcium dependence. However, mannan did not inhibit SP-A binding, suggesting that binding is mediated by a direct protein-protein interaction that does not involve carbohydrate recognition. Our laboratory has previously shown that SP-A is rapidly endocytosed by human MPhi into discrete vesicles. Although previous work indicates that SP-A is ultimately degraded by murine MPhi over time, the trafficking pathway of SP-A through MPhi after uptake has not been reported and is of potential biological importance. We examined trafficking of SP-A in human MPhi by electron and confocal microscopy and show for the first time that SP-A is endocytosed by primary human MPhi through clathrin-coated pits and colocalizes sequentially over time with the early endosome marker EEA1, late endosome marker lamp-1, and lysosome marker cathepsin D. We conclude that SP-A binds to receptor(s) on human MPhi, is endocytosed by a receptor-mediated, clathrin-dependent process, and trafficks through the endolysosomal pathway. These studies provide further insight into the interactions of SP-A with the MPhi cell surface and intracellular compartments that play important roles in SP-A modulation of lung MPhi biology.
机译：在非发炎的肺中，表面活性剂蛋白A（SP-A）通过影响巨噬细胞（MPhi）功能，调节细胞因子以及活性氧和氮中间产物而充当抗炎分子。尽管已经描述了SP-A与几种蛋白质的结合，但是负责SP-A对人MPhi的这些作用的受体尚不清楚。在这项研究中，我们证明了SP-A与原代人MPhi的高亲和力特异性结合。 EGTA抑制SP-A的结合，表明钙依赖性。但是，甘露聚糖并没有抑制SP-A的结合，这表明结合是由不涉及碳水化合物识别的直接蛋白质-蛋白质相互作用所介导的。我们的实验室以前已经证明，SP-A被人的MPhi迅速内吞成离散的囊泡。尽管先前的工作表明SP-A最终会随着时间的流逝而被鼠类MPhi降解，但尚未报道SP-A在摄取后通过MPhi的转运途径，具有潜在的生物学重要性。我们通过电子显微镜和共聚焦显微镜检查了人MPhi中SP-A的运输，并首次显示SP-A被初生人MPhi通过网格蛋白包被的凹坑内吞，并随时间顺序与早期内体标记物EEA1，内体晚期共定位。标记灯1和溶酶体标记组织蛋白酶D。我们得出结论，SP-A与人MPhi上的受体结合，被受体介导的网格蛋白依赖性过程吞噬，并通过溶酶体途径贩运。这些研究为SP-A与MPhi细胞表面和细胞内区室的相互作用提供了进一步的见识，这些相互作用在SP-A调节肺MPhi生物学中起着重要作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号