Clearance of apoptotic photoreceptors -: Elimination of apoptotic debris into the subretinal space and macrophage-mediated phagocytosis via phosphatidylserine receptor and integrin αvβ3
Clearance of apoptotic photoreceptors -: Elimination of apoptotic debris into the subretinal space and macrophage-mediated phagocytosis via phosphatidylserine receptor and integrin αvβ3
复制标题
DOI：
10.1016/s0002-9440(10)64321-0
复制
发表时间：
2003-06-01
影响因子：
6
通讯作者：
Kroemer, G
中科院分区：
文献类型：
--
作者：
Hisatomi, T;Sakamoto, T;Kroemer, G
细胞凋亡碎片的有效吞噬清除是细胞凋亡过程中神经组织维持的基础。视网膜脱离后视网膜光感受器发生凋亡。尽管它们的细胞凋亡诱导阶段已得到充分讨论，但它们的吞噬过程仍相当不清楚。我们在此证明，凋亡的光感受器被选择性地从其生理定位（外核层）消除到视网膜下空间，然后被单核细胞衍生的巨噬细胞吞噬。这可以通过超微结构和免疫表型分析来证明。此外，在骨髓来源的细胞中表达转基因绿色荧光蛋白的嵌合体小鼠中，在视网膜脱离诱导光感受器凋亡后可以检测到巨噬细胞的局部浸润。局部注射阻断磷脂酰丝氨酸受体（PSR）的抗体或阻断整合素αvβ3的肽（GRGDSP）表明吞噬清除涉及体内的PSR以及整合素αvβ3。重要的是，用这些试剂获得的阻断水平是不同的。尽管抗 PSR 增加了无法与巨噬细胞结合的凋亡细胞的频率，但 GRGDSP 阻止了巨噬细胞吞噬（但不是识别）凋亡的感光细胞。据我们所知，这是第一份描述凋亡光感受器的机制的报告；通过视网膜下空间中的定向过程选择性地消除。
The effective phagocytotic clearance of apoptotic debris is fundamental to the maintenance of neural tissues during apoptosis. Retinal photoreceptors undergo apoptosis after retinal detachment. Although their induction phase of apoptosis has been well discussed, their phagocytotic process remains quite unclear. We herein demonstrate that apoptotic photoreceptors are selectively eliminated from their physiological localization, the outer nuclear layer, to the subretinal space, and then phagocytosed by monocyte-derived macrophages. This could be shown by an ultrastructural and immunophenotypic analysis. Moreover, in chimera mice expressing transgenic green fluorescent protein in bone marrow-derived cells, the local infiltration of macrophages could be detected after retinal detachment-induced photoreceptor apoptosis. The local injection of an antibody blocking the phosphatidylserine receptor (PSR) or a peptide (GRGDSP)-blocking integrin alphavbeta3 revealed that phagocytotic clearance involves the PSR as well as integrin alphavbeta3 in vivo. Importantly, the level of blockade obtained with these reagents was different. Although anti-PSR increased the frequency of apoptotic cells that fail to bind to macrophages, GRGDSP prevented the engulfment (but not the recognition) of apoptotic photoreceptor cells by macrophages. To our knowledge, this is the first report describing the mechanisms through which apoptotic photoreceptors; are selectively eliminated via a directional process in the subretinal space.