A Rab11-containing rapidly recycling compartment in macrophages that promotes phagocytosis
A Rab11-containing rapidly recycling compartment in macrophages that promotes phagocytosis
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DOI：
10.1073/pnas.97.2.680
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发表时间：
2000-01-18
影响因子：
11.1
通讯作者：
Greenberg, S
中科院分区：
文献类型：
--
作者：
Cox, D;Lee, DJ;Greenberg, S
巨噬细胞是免疫系统的特化细胞，具有巨大的吞噬能力。巨噬细胞在吞噬过程中内化其质膜的大部分的能力表明它们具有快速更新质膜的机制。我们研究了内吞膜再循环在促进吞噬作用中的作用。与许多其他细胞类型相比，巨噬细胞缺乏形态学上不同的中心粒周围再循环室，而是表现出广泛的转铁蛋白受体阳性小管和囊泡网络参与再循环。巯基乙酸盐诱导的小鼠腹腔巨噬细胞（硫代巨噬细胞）中转铁蛋白再循环的速率非常快，其胞吐速率常数比大多数其他细胞高2- 3倍。由于GTTRab 11与其他细胞中的转铁蛋白再循环有关，我们确定了它在转铁蛋白再循环和巨噬细胞吞噬中的作用。表达表位标记的Rab 11的巨噬细胞表明Rab 11存在于几个细胞内膜区室中，包括内体和新生吞噬体。Rab 11的CTP结合缺陷等位基因Rab 11 25 N的表达导致转铁蛋白流出速率降低和Fc（γ）R介导的吞噬作用受损，其中Fc（γ）R是IgC的Fc部分的受体。与此相反，Rab 11 70 L，一个GTP酶缺陷的等位基因Rab 11的表达，导致转铁蛋白流出率增加，增强吞噬作用。我们的结论是，巨噬细胞已经适应了一个快速动员，内吞隔室，以增强吞噬作用。Rab 11参与将该隔室募集到巨噬细胞表面。
Macrophages are specialized cells of the immune system that exhibit a prodigious capacity for phagocytosis. The ability of macrophages to internalize a substantial proportion of their plasma membrane during phagocytosis indicates that they possess a mechanism for the rapid renewal of plasma membrane. We examined the role of endocytic membrane recycling in promoting phagocytosis. In contrast to many other cell types, macrophages lack a morphologically distinct peri-centriolar recycling compartment but instead demonstrate an extensive network of transferrin receptor-positive tubules and vesicles that participated in recycling. The rate of transferrin recycling in thioglycollate-elicited murine peritoneal macrophages (thio-macrophages) was exceedingly rapid, with exocytic rate constants that were 2- to 3-fold higher than those of most other cells. Because the GTPase Rab11 has been implicated in transferrin recycling in other cells, we determined its role in transferrin recycling and phagocytosis in macrophages. Macrophages expressing epitope-tagged Rab11 demonstrated the presence of Rab11 in several intracellular membrane compartments, including endosomes and nascent phagosomes, Expression of Rab11 25N, a CTP binding-deficient allele of Rab11, led to a decreased rate of transferrin efflux and impaired Fc(gamma)R-mediated phagocytosis, where Fc(gamma)R is the receptor for the Fc portion of IgC. In contrast, expression of Rab11 70L, a GTPase-deficient allele of Rab11, led to an increased rate of transferrin efflux and enhanced phagocytosis. We conclude that macrophages have adapted a rapidly mobilizable, endocytic compartment to enhance phagocytosis. Rab11 participates in the recruitment of this compartment to the macrophage cell surface.