Macrophages clear refrigerator storage-damaged red blood cells and subsequently secrete cytokines in vivo, but not in vitro, in a murine model.
Macrophages clear refrigerator storage-damaged red blood cells and subsequently secrete cytokines in vivo, but not in vitro, in a murine model.
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DOI：
10.1111/trf.12755
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发表时间：
2014-12
期刊：
影响因子：
2.9
通讯作者：
Spitalnik SL
中科院分区：
文献类型：
--
作者：
Wojczyk BS;Kim N;Bandyopadhyay S;Francis RO;Zimring JC;Hod EA;Spitalnik SL
在小鼠中，冰箱储存的红细胞（rbc）被血管外溶血清除并诱导细胞因子的产生。为了加强对这一现象的理解，我们试图在体外建立模型。使用J774A.1小鼠巨噬细胞和原代小鼠脾巨噬细胞，研究了冰箱储存的小鼠红细胞的摄食和随后的细胞因子产生。使用野生型和ccl2 - gfp报告小鼠进行体内红细胞清除。虽然J774A.1细胞和原代巨噬细胞在体外优先摄取冷藏保存的红细胞，但与新鲜分离的红细胞相比，两者在红细胞吞噬作用后都没有产生增加的细胞因子。相比之下，体内冷藏红细胞吞噬诱导循环单核细胞趋化蛋白-1 （MCP-1）和角化细胞趋化蛋白（KC）增加，相应地增加小鼠脾脏和肝脏mRNA水平。在脾脏中，这些主要由CD11b+细胞表达。使用ccl2 - gfp报告小鼠，负责MCP-1 mRNA产生的主要脾细胞群是组织内巨噬细胞（即CD45+， CD11b+, F4/80+, Ly6c+， CD11clow细胞）。J774A.1细胞和原代巨噬细胞通过吞噬作用选择性摄入冷藏红细胞。虽然细胞因子的表达没有增强，但这种方法可以用来鉴定相关的受体-配体组合。相比之下，细胞因子水平升高后，吞噬冰箱储存的红细胞在体内。这些主要在肝脏和脾脏中被清除，这表明MCP-1和KC mRNA表达增加。最后，在小鼠脾脏中，组织常驻巨噬细胞主要参与MCP-1 mRNA的产生。细胞因子在体外和体内产生的差异尚不清楚。
In mice, refrigerator-stored red blood cells (RBCs) are cleared by extravascular hemolysis and induce cytokine production. To enhance understanding of this phenomenon, we sought to model it in vitro. Ingestion of refrigerator-stored murine RBCs and subsequent cytokine production were studied using J774A.1 mouse macrophage cells and primary murine splenic macrophages. Wild-type and Ccl2-GFP-reporter mice were used for RBC clearance in vivo. Although J774A.1 cells and primary macrophages preferentially ingested refrigerator-stored RBCs in vitro, as compared to freshly-isolated RBCs, neither produced increased cytokines following erythrophagocytosis. In contrast, phagocytosis of refrigerator-stored RBCs in vivo induced increases in circulating monocyte chemoattractant protein-1 (MCP-1) and keratinocyte chemoattractant (KC), and correspondingly increased mRNA levels in mouse spleen and liver. In the spleen, these were predominantly expressed by CD11b+ cells. Using Ccl2-GFP-reporter mice, the predominant splenic population responsible for MCP-1 mRNA production were tissue-resident macrophages (i.e., CD45+, CD11b+, F4/80+, Ly6c+, CD11clow cells). J774A.1 cells and primary macrophages selectively ingested refrigerator-stored RBCs by phagocytosis. Although cytokine expression was not enhanced, this approach could be used to identify the relevant receptor-ligand combination(s). In contrast, cytokine levels increased following phagocytosis of refrigerator-stored RBCs in vivo. These were primarily cleared in the liver and spleen, which demonstrated increased MCP-1 and KC mRNA expression. Finally, in mouse spleen, tissue-resident macrophages were predominantly involved in MCP-1 mRNA production. The differences between cytokine production in vitro and in vivo are not yet well understood.
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DOI：
10.1074/jbc.m110.203398
发表时间：
2011-08-05
期刊：
The Journal of biological chemistry
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Bennett-Guerrero, Elliott
影响因子：
1.5
作者：
Dzik, W.
通讯作者：
Dzik, W.
影响因子：
3.1
作者：
KELLY, KA;HILL, MR;GIMBLE, JM
通讯作者：
GIMBLE, JM
DOI：
10.1038/nri3073
发表时间：
2011-10-14
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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