Early rise in inflammation and microcirculatory disorder determine the development of autoimmune pancreatitis in the MRL/Mp-mouse.
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. < or =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.
Sorg
Heiko
H
Institute for Experimental Surgery, Division of Gastroenterology, University of Rostock, Rostock, Germany.
Lorch
Benjamin
B
Jaster
Robert
R
Fitzner
Brit
B
Ibrahim
Saleh
S
Holzhueter
Stephanie-Anna
SA
Nizze
Horst
H
Vollmar
Brigitte
B
D000818:Animals; D000974:Antibodies, Antinuclear / Q000378:metabolism; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008833:Microcirculation / Q000502:physiology*; D010179:Pancreas / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000209:etiology* / Q000276:immunology / Q000473:pathology
D000974:Antibodies, Antinuclear