title: Dendritic cells promote pancreatic viability in mice with acute pancreatitis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  DCs are required for pancreatic viability in mice with acute pancreatitis and might protect organs against cell stress.
authors.affiliation: S. Arthur Localio Laboratory, Department of Surgery, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Bedrosian
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Nguyen
authors.forename: Michael
authors.initials: M
authors.lastname: Hackman
authors.forename: Michael K
authors.initials: MK
authors.lastname: Connolly
authors.forename: Ashim
authors.initials: A
authors.lastname: Malhotra
authors.forename: Junaid
authors.initials: J
authors.lastname: Ibrahim
authors.forename: Napoleon E
authors.initials: NE
authors.lastname: Cieza-Rubio
authors.forename: Justin R
authors.initials: JR
authors.lastname: Henning
authors.forename: Rocky
authors.initials: R
authors.lastname: Barilla
authors.forename: Adeel
authors.initials: A
authors.lastname: Rehman
authors.forename: H Leon
authors.initials: HL
authors.lastname: Pachter
authors.forename: Marco V
authors.initials: MV
authors.lastname: Medina-Zea
authors.forename: Steven M
authors.initials: SM
authors.lastname: Cohen
authors.forename: Alan B
authors.initials: AB
authors.lastname: Frey
authors.forename: Devrim
authors.initials: D
authors.lastname: Acehan
authors.forename: George
authors.initials: G
authors.lastname: Miller
mesh_terms: D000208:Acute Disease; D000818:Animals; D001120:Arginine / Q000009:adverse effects; D002108:Ceruletide / Q000009:adverse effects; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D004167:Diphtheria Toxin / Q000494:pharmacology; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000473:pathology* / Q000503:physiopathology*; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D010641:Phenotype; D013997:Time Factors; D014022:Tissue Survival / Q000502:physiology*
chemical_list: D004167:Diphtheria Toxin; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D015850:Interleukin-6; D002108:Ceruletide; D001120:Arginine