The "Phagocytic Synapse" and Clearance of Apoptotic Cells.
The "Phagocytic Synapse" and Clearance of Apoptotic Cells.
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DOI：
10.3389/fimmu.2017.01708
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发表时间：
2017
影响因子：
7.3
通讯作者：
Dransfield I
中科院分区：
文献类型：
--
作者：
Barth ND;Marwick JA;Vendrell M;Rossi AG;Dransfield I
细胞凋亡和随后的细胞吞噬清除对于胚胎发育、需要定期细胞更新的组织的维持和先天免疫是重要的。及时清除凋亡细胞可防止继发性坏死和细胞内容物的释放，防止细胞应激和炎症。此外，凋亡细胞接触和吞噬后的吞噬细胞行为改变参与了抗炎表型，这影响了炎症和免疫反应的发展和进展。凋亡细胞清除缺陷是各种炎症性和自身免疫性疾病发生的基础。在介导细胞凋亡清除的受体中有相当多的功能冗余，突显了这一过程在不同生理过程中的重要性。单个吞噬细胞可以利用多个受体途径，有效地通过吞噬细胞(系留)捕获凋亡细胞，并随后启动内化所需的信号事件。在这篇综述中，我们将考虑与细胞凋亡相关的表面改变和分子调理事件，它们可能代表一个可调节的信号，以上下文相关的方式赋予不同的细胞内信号事件，从而产生特定的吞噬细胞反应。吞噬细胞和凋亡靶细胞之间的有效分子通讯可能需要合作受体的利用和泡泡细胞突触的建立，后者起到稳定黏附相互作用的作用，并促进控制吞噬细胞反应所需的信号平台的组织。
Apoptosis and subsequent phagocytic clearance of apoptotic cells is important for embryonic development, maintenance of tissues that require regular cellular renewal and innate immunity. The timely removal of apoptotic cells prevents progression to secondary necrosis and release of cellular contents, preventing cellular stress and inflammation. In addition, altered phagocyte behavior following apoptotic cell contact and phagocytosis engages an anti-inflammatory phenotype, which impacts upon development and progression of inflammatory and immune responses. Defective apoptotic cell clearance underlies the development of various inflammatory and autoimmune diseases. There is considerable functional redundancy in the receptors that mediate apoptotic cell clearance, highlighting the importance of this process in diverse physiological processes. A single phagocyte may utilize multiple receptor pathways for the efficient capture of apoptotic cells by phagocytes (tethering) and the subsequent initiation of signaling events necessary for internalization. In this review, we will consider the surface alterations and molecular opsonization events associated with apoptosis that may represent a tunable signal that confers distinct intracellular signaling events and hence specific phagocyte responses in a context-dependent manner. Efficient molecular communication between phagocytes and apoptotic targets may require cooperative receptor utilization and the establishment of efferocytic synapse, which acts to stabilize adhesive interactions and facilitate the organization of signaling platforms that are necessary for controlling phagocyte responses.