Dynamic macrophage "probing" is required for the efficient capture of phagocytic targets.
Dynamic macrophage "probing" is required for the efficient capture of phagocytic targets.
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DOI：
10.1083/jcb.201007056
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发表时间：
2010-12-13
期刊：
影响因子：
--
通讯作者：
Grinstein S
中科院分区：
文献类型：
--
作者：
Flannagan RS;Harrison RE;Yip CM;Jaqaman K;Grinstein S
巨噬细胞不是通过免疫受体被动地结合配体，而是通过反复延伸富含肌动蛋白的突起来捕获颗粒。免疫受体与配体的结合被认为是一个被动的随机过程。与这一观点相反，我们发现Fcγ受体与IgG调理颗粒的结合在巨噬细胞、树突状细胞和小胶质细胞中受到干扰肌动蛋白组装或分解的试剂的抑制。受体的横向流动性的变化-通过单粒子跟踪评估-或在膜的微弹性-通过原子力显微镜测定-不能解释肌动蛋白破坏对粒子结合的影响。相反，我们发现巨噬细胞通过主动延伸富含肌动蛋白的结构来接触它们的靶点。这些突起的形成由Rac驱动，并且需要磷脂酰肌醇4，5-二磷酸和磷脂酰肌醇3，4，5-三磷酸。捕获C3双调理以及unopsonized目标的巨噬细胞也依赖于肌动蛋白。因此，吞噬细胞以类似于树突状细胞对流体环境进行组成性取样的方式连续探测其环境中的外来颗粒。吞噬细胞的主动探测在面对几乎不调理和/或高度移动的靶标时是最重要的。
Rather than passively binding ligands via immunoreceptors, macrophages capture particles by repeated extension of actin-rich protrusions. Binding of ligands by immunoreceptors is thought to be a passive, stochastic process. Contrary to this notion, we found that binding of IgG-opsonized particles by Fcγ receptors was inhibited in macrophages, dendritic and microglial cells by agents that interfere with actin assembly or disassembly. Changes in the lateral mobility of the receptors—assessed by single-particle tracking—or in the microelasticity of the membrane—determined by atomic-force microscopy—could not account for the effects of actin disruption on particle binding. Instead, we found that the macrophages contact their targets by actively extending actin-rich structures. Formation of these protrusions is driven by Rac and requires phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. Capture of C3bi-opsonized as well as unopsonized targets by macrophages was also dependent on actin. Thus, phagocytes continuously probe their environment for foreign particles in a manner akin to the constitutive sampling of the fluid milieu by dendritic cells. Active probing by phagocytes is most important when confronted by scarcely opsonized and/or highly mobile targets.
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影响因子：
21.3
作者：
Côté, JF;Motoyama, AB;Vuori, K
通讯作者：
Vuori, K
影响因子：
4.1
作者：
Fleming, IN;Gray, A;Downes, CP
通讯作者：
Downes, CP
DOI：
10.1073/pnas.0702449104
发表时间：
2007-07-10
影响因子：
11.1
作者：
Kress, Holger;Stelzer, Ernst H. K.;Rohrbach, Alexander
通讯作者：
Rohrbach, Alexander
影响因子：
3.3
作者：
Hoppe, AD;Swanson, JA
通讯作者：
Swanson, JA
影响因子：
4.8
作者：
Kovács, M;Tóth, J;Sellers, JR
通讯作者：
Sellers, JR