Dendritic cells promote pancreatic viability in mice with acute pancreatitis.
Dendritic cells promote pancreatic viability in mice with acute pancreatitis.
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树突状细胞促进急性胰腺炎小鼠的胰腺生存力。
DOI：
10.1053/j.gastro.2011.07.033
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发表时间：
2011-11
期刊：
影响因子：
29.4
通讯作者：
Miller G
中科院分区：
文献类型：
--
作者：
Bedrosian AS;Nguyen AH;Hackman M;Connolly MK;Malhotra A;Ibrahim J;Cieza-Rubio NE;Henning JR;Barilla R;Rehman A;Pachter HL;Medina-Zea MV;Cohen SM;Frey AB;Acehan D;Miller G
急性胰腺炎增加器官坏死的发病率和死亡率，其机制尚不完全清楚。树突状细胞（DC）可以促进或抑制炎症，这取决于它们的亚型和背景。我们研究了DC在急性胰腺炎发生发展中的作用。用雨蛙肽或L-精氨酸诱导CD 11c. DTR小鼠急性胰腺炎;用白喉毒素耗竭DC。使用Kaplan-Meier分析来分析存活率。急性胰腺炎小鼠胰腺中MHC II + CD 11 c + DC的数量增加了100倍，占胰腺内白细胞的近15%。胰腺内DC在急性胰腺炎小鼠中获得免疫表型;它们表达更高水平的MHC II和CD86，并增加白细胞介素-6、膜辅因子蛋白（MCP）-1和肿瘤坏死因子（TNF）-α的产生。然而，而不是诱导器官破坏性的炎症过程中，DC所需的胰腺活力;外分泌胰腺死亡的小鼠，耗尽DC和雨蛙肽或L-精氨酸的挑战。所有患有胰腺炎的DC耗尽的小鼠在4天内死于腺泡细胞死亡。胰腺炎小鼠的DC耗竭导致中性粒细胞浸润和炎症的全身标志物水平增加。然而，与DC耗竭相关的器官坏死不需要浸润中性粒细胞、NF-κ B活化或丝裂原活化蛋白激酶或TNF-α信号传导。DC是急性胰腺炎小鼠胰腺存活所必需的，并可能保护器官免受细胞应激。
Acute pancreatitis increases morbidity and mortality from organ necrosis by mechanisms that are incompletely understood. Dendritic cells (DCs) can promote or suppress inflammation, depending on their subtype and context. We investigated the roles of DC in development of acute pancreatitis. Acute pancreatitis was induced in CD11c.DTR mice using caerulein or L-arginine; DCs were depleted by administration of diphtheria toxin. Survival was analyzed using Kaplan-Meier analysis. Numbers of MHC II+CD11c+DC increased 100-fold in pancreas of mice with acute pancreatitis, to account for nearly 15% of intra-pancreatic leukocytes. Intra-pancreatic DC acquired an immune phenotype in mice with acute pancreatitis; they expressed higher levels of MHC II and CD86 and increased production of interleukin-6, membrane cofactor protein (MCP)-1, and tumor necrosis factor (TNF)-α. However, rather than inducing an organ-destructive inflammatory process, DC were required for pancreatic viability; the exocrine pancreas died in mice that were depleted of DC and challenged with caerulein or L-arginine. All mice with pancreatitis that were depleted of DC died from acinar cell death within 4 days. Depletion of DC from mice with pancreatitis resulted in neutrophil infiltration and increased levels of systemic markers of inflammation. However, the organ necrosis associated with depletion of DC did not require infiltrating neutrophils, activation of NF-κB, or signaling by mitogen-activated protein kinase or TNF-α. DC are required for pancreatic viability in mice with acute pancreatitis and might protect organs against cell stress.
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影响因子：
32.4
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Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
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