Differential regulation of phagosome maturation in macrophages and dendritic cells mediated by Rho GTPases and ezrin-radixin-moesin (ERM) proteins
Differential regulation of phagosome maturation in macrophages and dendritic cells mediated by Rho GTPases and ezrin-radixin-moesin (ERM) proteins
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DOI：
10.1073/pnas.0605331103
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发表时间：
2006-08-22
影响因子：
11.1
通讯作者：
Henson, Peter M.
中科院分区：
文献类型：
--
作者：
Erwig, Lars-Peter;McPhilips, Kathleen A.;Henson, Peter M.
从组织中删除凋亡细胞涉及巨噬细胞、树突细胞和组织细胞对它们的吞噬作用。虽然很多注意力都集中在参与的配体，受体，和机制的摄取，很少有人知道的处置摄入的细胞内的吞噬体。在这里，我们表明，凋亡细胞的巨噬细胞或成纤维细胞的吞噬体快速成熟的结果，而巨噬细胞吞噬体含有1g-调理的靶细胞成熟的速度较慢。早期成熟被证明依赖于通过Rho激酶作用于ezrin-radixin-moesin蛋白的Rho激活。阻断Rho信号传导或抑制膜突蛋白都延迟了与调理剂靶点相比的成熟率。相比之下，树突状细胞中的吞噬体成熟较慢，凋亡和调理的靶细胞之间相似，并且不受Rho抑制的影响。这些观察结果对死亡细胞的清除以及不同吞噬细胞在抗原消化和呈递中所起的作用具有直接影响。
Deletion of apoptotic cells from tissues involves their phagocytosis by macrophages, dendritic cells, and tissue cells. Although much attention has been focused on the participating ligands, receptors, and mechanisms of uptake, little is known of the disposition of the ingested cell within the phagosome. Here we show that uptake of apoptotic cells by macrophages or fibroblasts results in rapid phagosome maturation, whereas macrophage phagosomes containing 1g-opsonized target cells mature at a slower rate. The early maturation was shown to depend on activation of Rho acting through Rho kinase on ezrin-radixin-moesin proteins. Blockade of Rho signaling or inhibition of moesin both delayed maturation rates to those seen with opsonized targets. By contrast, phagosome maturation in dendritic cells was slower, similar between apoptotic and opsonized target cells, and unaffected by Rho inhibition. These observations have direct implications for the clearance of dying cells and the roles played by different phagocytes in antigen digestion and presentation.