Hepatocyte transplantation-induced liver inflammation is driven by cytokines-chemokines associated with neutrophils and Kupffer cells.
Hepatocyte transplantation-induced liver inflammation is driven by cytokines-chemokines associated with neutrophils and Kupffer cells.
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DOI：
10.1053/j.gastro.2009.01.063
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发表时间：
2009-05
期刊：
影响因子：
29.4
通讯作者：
Gupta S
中科院分区：
文献类型：
--
作者：
Krohn N;Kapoor S;Enami Y;Follenzi A;Bandi S;Joseph B;Gupta S
肝细胞移植诱导的肝脏炎症损害细胞植入。我们确定了促炎细胞因子和趋化因子是否在肝细胞移植的调节中发挥作用。我们在大鼠肝细胞移植系统中进行了长达三周的研究。通过实时定量聚合酶链反应研究了84个精氨酸趋化因子基因的表达。通过免疫组织化学验证所选上调基因的表达。通过髓过氧化物酶活性测定证明了中性粒细胞的肝脏募集，通过碳吞噬测定建立了枯否细胞活化。通过细胞耗竭研究确定中性粒细胞和枯否细胞在调节嗜中性粒细胞趋化因子基因表达以及细胞植入中的作用。在同基因细胞移植后6小时内，25种丝氨酸-趋化因子基因的表达增加了2至123倍，p<0.05。这些基因主要与活化的中性粒细胞和巨噬细胞相关，包括趋化因子配体CXCL 1、CXCL 2、CCL 3、CCL 4，趋化因子受体CXCR 1或CXCR 2、CCR 1、CCR 2以及调节细胞因子TNF-α和IL 6。肝脏中的炎性细胞对CCR 1、CCR 2、CXCR 1和CXCR 2进行免疫染色，这表明上调的mRNA被适当翻译。当中性粒细胞和枯否细胞分别用中性粒细胞抗血清和氯化钆耗竭时，在移植细胞之前，细胞移植诱导的趋化因子应答减弱。几乎所有异常消退的动物与中性粒细胞抗血清加氯化钆治疗。此外，中性粒细胞或枯否细胞的耗竭改善了移植细胞的植入。细胞移植诱导的肝脏炎症涉及能够由中性粒细胞和枯否细胞调节的促炎性趋化因子系统。这为优化细胞治疗策略提供了新的方向。
Hepatocyte transplantation-induced liver inflammation impairs cell engraftment. We defined whether proinflammatory cytokines and chemokines played roles in regulation of hepatocyte engraftment in the liver. We performed studies over up to three weeks in rat hepatocyte transplantation systems. Expression of 84 cytokine-chemokine genes was studied by quantitative real-time polymerase chain reactions. Expression of selected upregulated genes was verified by immunohistochemistry. Hepatic recruitment of neutrophils was demonstrated by myeloperoxidase activity assays and Kupffer cell activation was established by carbon phagocytosis assays. The role of neutrophils and Kupffer cells in regulating expression of cytokine-chemokine genes as well as cell engraftment was determined by cell depletion studies. Within six hours after syngeneic cell transplantation, expression of 25 cytokine-chemokine genes increased by 2- to 123-fold, p<0.05. These genes were largely associated with activated neutrophils and macrophages, including chemokine ligands, CXCL1, CXCL2, CCL3, CCL4, chemokine receptors, CXCR1 or CXCR2, CCR1, CCR2, and regulatory cytokines TNF-α and IL6. Inflammatory cells in the liver immunostained for CCR1, CCR2, CXCR1 and CXCR2, which indicated that upregulated mRNAs were appropriately translated. When neutrophils and Kupffer cells were depleted with neutrophil anti-serum and gadolinium chloride, respectively, before transplanting cells, cell transplantation-induced cytokine-chemokine responses were attenuated. Virtually all abnormalities subsided in animals treated with neutrophil anti-serum plus gadolinium chloride. Moreover, depletion of neutrophils or Kupffer cells improved engraftment of transplanted cells. Cell transplantation-induced liver inflammation involves proinflammatory cytokine-chemokine systems capable of modulation by neutrophils and Kupffer cells. This offers new directions for optimizing cell therapy strategies.
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影响因子：
13.5
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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DOI：
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发表时间：
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影响因子：
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