Early rise in inflammation and microcirculatory disorder determine the development of autoimmune pancreatitis in the MRL/Mp-mouse

Heiko Sorg, Benjamin Lorch, Robert Jaster, Brit Fitzner, Saleh Ibrahim, Stephanie Anna Holzhueter, Horst Nizze, Brigitte Vollmar

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Autoimmune pancreatitis (AIP) is a rare cause of chronic pancreatitis and mimics pancreatic cancer. Although there is strong interest in research, etiology and pathophysiology of AIP are still unknown. Therefore, we analyzed a total of 92 MRL/Mp-mice of either sex, which are prone to develop AIP, in four different age groups (8-12, 16-20, 24-28, and 32-40 wk). Using intravital fluorescence microscopy, histology, laboratory analysis, and Western blot, onset, severity, and pathophysiological mechanisms of AIP were evaluated. Female animals showed in vivo an age-dependent increase of intrapancreatic leukocyte accumulation, as well as a loss in functional capillary perfusion. In contrast, intrapancreatic inflammation in male mice was less pronounced and not age dependent. Furthermore, pancreatic tissue specimen of female animals exhibited major organ destruction with significantly higher values of mean pathological scores (1.5 ± 0.3 vs. ≤0.2; P < 0.05), as well as significantly increased CD4-, CD8-, CD11b-, and CD138-positive cells compared with male animals of the same age. Interestingly, there was a significant positive correlation between intravascular leukocyte adherence and the histopathological score of the pancreas, indicating a determining role of the innate immune system for the late onset of AIP. The present study shows that the onset of AIP is characterized by an inflammatory response and microcirculatory failure, most probably constituting initiators and propagators of this autoimmune disease.

Original languageBritish English
Pages (from-to)G1274-G1280
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume295
Issue number6
DOIs
StatePublished - Dec 2008

Keywords

  • Intravital microscopy
  • Leukocytes
  • Perfusion failure

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