Dendritic cells promote pancreatic viability in mice with acute pancreatitis

Andrea S. Bedrosian, Andrew H. Nguyen, Michael Hackman, Michael K. Connolly, Ashim Malhotra, Junaid Ibrahim, Napoleon E. Cieza-Rubio, Justin R. Henning, Rocky Barilla, Adeel Rehman, H. Leon Pachter, Marco V. Medina-Zea, Steven M. Cohen, Alan B. Frey, Devrim Acehan, George Miller

Research output: Contribution to journalArticle

Abstract

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. 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.

Original languageEnglish (US)
Pages (from-to)1915-1926
Number of pages12
JournalGastroenterology
Volume141
Issue number5
DOIs
StatePublished - Nov 2011
Externally publishedYes

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Pancreatitis
Dendritic Cells
Ceruletide
Major Histocompatibility Complex
Arginine
CD46 Antigens
Tumor Necrosis Factor-alpha
Inflammation
Diphtheria Toxin
Exocrine Pancreas
Neutrophil Infiltration
Acinar Cells
Mitogen-Activated Protein Kinases
Interleukin-8
Pancreas
Interleukin-6
Leukocytes
Cell Death
Necrosis
Phenotype

Keywords

  • IL-6
  • Immune Response
  • MCP-1
  • Regulation
  • Suppression

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Bedrosian, A. S., Nguyen, A. H., Hackman, M., Connolly, M. K., Malhotra, A., Ibrahim, J., ... Miller, G. (2011). Dendritic cells promote pancreatic viability in mice with acute pancreatitis. Gastroenterology, 141(5), 1915-1926. https://doi.org/10.1053/j.gastro.2011.07.033

Dendritic cells promote pancreatic viability in mice with acute pancreatitis. / Bedrosian, Andrea S.; Nguyen, Andrew H.; Hackman, Michael; Connolly, Michael K.; Malhotra, Ashim; Ibrahim, Junaid; Cieza-Rubio, Napoleon E.; Henning, Justin R.; Barilla, Rocky; Rehman, Adeel; Pachter, H. Leon; Medina-Zea, Marco V.; Cohen, Steven M.; Frey, Alan B.; Acehan, Devrim; Miller, George.

In: Gastroenterology, Vol. 141, No. 5, 11.2011, p. 1915-1926.

Research output: Contribution to journalArticle

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 2011, 'Dendritic cells promote pancreatic viability in mice with acute pancreatitis', Gastroenterology, vol. 141, no. 5, pp. 1915-1926. https://doi.org/10.1053/j.gastro.2011.07.033
Bedrosian AS, Nguyen AH, Hackman M, Connolly MK, Malhotra A, Ibrahim J et al. Dendritic cells promote pancreatic viability in mice with acute pancreatitis. Gastroenterology. 2011 Nov;141(5):1915-1926. https://doi.org/10.1053/j.gastro.2011.07.033
Bedrosian, Andrea S. ; Nguyen, Andrew H. ; Hackman, Michael ; Connolly, Michael K. ; Malhotra, Ashim ; Ibrahim, Junaid ; Cieza-Rubio, Napoleon E. ; Henning, Justin R. ; Barilla, Rocky ; Rehman, Adeel ; Pachter, H. Leon ; Medina-Zea, Marco V. ; Cohen, Steven M. ; Frey, Alan B. ; Acehan, Devrim ; Miller, George. / Dendritic cells promote pancreatic viability in mice with acute pancreatitis. In: Gastroenterology. 2011 ; Vol. 141, No. 5. pp. 1915-1926.
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AU - Rehman, Adeel

AU - Pachter, H. Leon

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