Physiologically aged red blood cells undergo erythrophagocytosis in vivo but not in vitro
Physiologically aged red blood cells undergo erythrophagocytosis in vivo but not in vitro
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DOI：
10.3324/haematol.2011.057620
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发表时间：
2012-07-01
期刊：
影响因子：
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通讯作者：
Meyron-Holtz, Esther G.
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文献类型：
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作者：
Gottlieb, Yehonatan;Topaz, Orit;Meyron-Holtz, Esther G.
研究背景红细胞的寿命在巨噬细胞通过吞噬红细胞的作用清除衰老红细胞时终止。这使得巨噬细胞除了在组织重塑和先天免疫中发挥作用外，还处于全身铁循环的中心。到目前为止，通过评估被破坏以模拟衰老的红细胞的吞噬作用来研究红细胞吞噬作用。这些研究表明，收购一些特定的个人衰老标志物可以触发巨噬细胞的红细胞吞噬作用，但我们假设，这种受损的红细胞的红细胞吞噬作用的机制可能不同于生理老化的红细胞的红细胞吞噬作用。设计和MethodsTo测试这一假设，我们产生了一个红细胞群体高度富集在衰老的红细胞在小鼠中的超输血程序。各种红细胞老化的信号进行了分析和红细胞吞噬作用进行了评估，在体内和vitro.ResultsThe大队列的衰老的红细胞从hypertransfused小鼠进行了许多相同的老化信号从对照小鼠的衰老的红细胞。将来自高输血小鼠的荧光标记红细胞注射到未处理小鼠中的吞噬作用远高于来自对照小鼠的标记红细胞的吞噬作用。然而，无论是红细胞从hypertransfused小鼠，也不是那些从对照小鼠被吞噬在体外由初级巨噬细胞cultures，即使这些文化能够吞噬氧化损伤的红细胞。ConclusionsThe大衰老的红细胞群hypertransfused小鼠模仿生理老化的红细胞。对于这些衰老红细胞的有效红细胞吞噬作用，巨噬细胞依赖于完整吞噬组织的一些特征来支持。
BackgroundThe lifespan of red blood cells is terminated when macrophages remove senescent red blood cells by erythrophagocytosis. This puts macrophages at the center of systemic iron recycling in addition to their functions in tissue remodeling and innate immunity. Thus far, erythrophagocytosis has been studied by evaluating phagocytosis of erythrocytes that were damaged to mimic senescence. These studies have demonstrated that acquisition of some specific individual senescence markers can trigger erythrophagocytosis by macrophages, but we hypothesized that the mechanism of erythrophagocytosis of such damaged erythrocytes might differ from erythrophagocytosis of physiologically aged erythrocytes.Design and MethodsTo test this hypothesis we generated an erythrocyte population highly enriched in senescent erythrocytes by a hypertransfusion procedure in mice. Various erythrocyte-aging signals were analyzed and erythrophagocytosis was evaluated in vivo and in vitro.ResultsThe large cohort of senescent erythrocytes from hypertransfused mice carried numerous aging signals identical to those of senescent erythrocytes from control mice. Phagocytosis of fluorescently-labeled erythrocytes from hypertransfused mice injected into untreated mice was much higher than phagocytosis of labeled erythrocytes from control mice. However, neither erythrocytes from hypertransfused mice, nor those from control mice were phagocytosed in vitro by primary macrophage cultures, even though these cultures were able to phagocytose oxidatively damaged erythrocytes.ConclusionsThe large senescent erythrocyte population found in hypertransfused mice mimics physiologically aged erythrocytes. For effective erythrophagocytosis of these senescent erythrocytes, macrophages depend on some features of the intact phagocytosing tissue for support.