S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York 10016, USA.
Gastroenterology. 2011 Nov;141(5):1915-26.e1-14. doi: 10.1053/j.gastro.2011.07.033. Epub 2011 Jul 27.
BACKGROUND & AIMS: The cellular mediators of acute pancreatitis 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 method.
Numbers of major histocompatibility complex II(+)CD11c(+) DCs increased 100-fold in pancreata of mice with acute pancreatitis to account for nearly 15% of intrapancreatic leukocytes. Intrapancreatic DCs acquired a distinct immune phenotype in mice with acute pancreatitis; they expressed higher levels of major histocompatibility complex II and CD86 and increased production of interleukin-6, membrane cofactor protein-1, and tumor necrosis factor-α. However, rather than inducing an organ-destructive inflammatory process, DCs were required for pancreatic viability; the exocrine pancreas died in mice that were depleted of DCs and challenged with caerulein or L-arginine. All mice with pancreatitis that were depleted of DCs died from acinar cell death within 4 days. Depletion of DCs from mice with pancreatitis resulted in neutrophil infiltration and increased levels of systemic markers of inflammation. However, the organ necrosis associated with depletion of DCs did not require infiltrating neutrophils, activation of nuclear factor-κB, or signaling by mitogen-activated protein kinase or tumor necrosis factor-α.
DCs are required for pancreatic viability in mice with acute pancreatitis and might protect organs against cell stress.
急性胰腺炎的细胞介质尚不完全清楚。树突状细胞（DC）可根据其亚型和所处环境促进或抑制炎症。我们研究了 DC 在急性胰腺炎发病机制中的作用。
采用 CAER 或 L-精氨酸诱导 CD11c.DTR 小鼠发生急性胰腺炎；通过给予白喉毒素耗竭 DC。采用 Kaplan-Meier 法分析生存率。
急性胰腺炎小鼠胰腺内主要组织相容性复合体 II（+）CD11c（+）DC 数量增加 100 倍，占胰腺内白细胞的近 15%。急性胰腺炎小鼠胰腺内 DC 获得独特的免疫表型；它们表达更高水平的主要组织相容性复合体 II 和 CD86，并增加白细胞介素-6、膜辅助蛋白-1 和肿瘤坏死因子-α的产生。然而，DC 并非引发器官破坏性炎症过程，而是胰腺存活所必需的；用 CAER 或 L-精氨酸处理耗竭 DC 的小鼠，外分泌胰腺死亡。所有耗竭 DC 的胰腺炎小鼠在 4 天内死于腺泡细胞死亡。从胰腺炎小鼠中耗竭 DC 会导致中性粒细胞浸润和全身性炎症标志物水平升高。然而，耗竭 DC 引起的器官坏死并不需要浸润的中性粒细胞、核因子-κB 的激活或丝裂原活化蛋白激酶或肿瘤坏死因子-α的信号传导。
DC 是急性胰腺炎小鼠胰腺存活所必需的，可能保护器官免受细胞应激。
