Systemic lymphocyte activation modulates the severity of diet-induced acute pancreatitis in mice.
To examine the role of lymphocyte activation in the development of local and systemic complications in acute pancreatitis, we compared disease severity of choline-deficient, 0.5% ethionine supplemented (CDE) diet-induced acute pancreatitis in T- and B-cell deficient SCID mice and immunocompetent C.B-17 mice. Twenty-five female SCID and 17 female C.B-17 mice were fasted for 24 h and fed a CDE diet for 72 h. Twenty SCID and 12 C.B-17 mice were bled and their organs removed for histologic evaluation. Five control animals of both kinds were fed a regular diet for 6 days. Lung, kidney, and pancreas were examined microscopically, and pancreatic damage scored. Apoptosis was detected by DNA nick-end labeling and confirmed by DNA laddering. Trypsinogen-activation peptide was measured by enzyme-linked immunosorbent assay (ELISA), and the catalytic activity of PLA2 was determined by a radiometric assay. Four-day mortality was 10% in SCID and 33% in C.B-17 mice, and 10-day mortality was 0 in SCID and 60% in C.B-17 mice. SCID mice had mild pulmonary damage, whereas pulmonary injury was severe in C.B-17 mice. Pancreatic damage was severe in both groups. Even though in situ staining of apoptotic cells was found in all pancreatitis animals, apoptosis was confirmed by DNA laddering only in C.B-17 mice. In SCID mice, apoptotic cell staining positively correlated with necrosis (r = 0.91; p < 0.001). Plasma TAP and PLA2 catalytic activity did not differ significantly between the groups. In conclusion, the absence of T and B lymphocytes prevents severe pulmonary injury resulting from acute pancreatitis but does not influence pancreatic or renal damage. Our results suggest that systemic lymphocyte activation does not affect the initiating events that trigger pancreatic injury but modulates the systemic response, in particular, pulmonary injury caused by acute pancreatitis.
Department of General Surgery, University of Ulm, Germany.
J
J
Mayer
V J
VJ
Laine
B
B
Rau
H G
HG
Hotz
T
T
Foitzik
T J
TJ
Nevalainen
H G
HG
Beger
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D002796:Choline Deficiency / Q000150:complications; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D016513:Mice, SCID; D009842:Oligopeptides / Q000097:blood; D010195:Pancreatitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D016511:Severe Combined Immunodeficiency / Q000378:metabolism / Q000503:physiopathology*
D009842:Oligopeptides; C080396:trypsinogen activation peptide; D010741:Phospholipases A; D054467:Phospholipases A2