Cd40 ligand-deficient mice are protected against cerulein-induced acute pancreatitis and pancreatitis-associated lung injury.
OBJECTIVE
The interactions between inflammatory cells and their mediators play important roles in many inflammatory processes, but their importance during acute experimental pancreatitis and pancreatitis-associated lung injury is unclear. To address the role of the interaction between CD40 and its ligand CD40L, molecules that mediate major immunoregulatory functions, pancreatitis was induced by administering supramaximal doses of cerulein in mice that do not express CD40L.


METHODS
The severity of pancreatitis was measured by serum amylase activity, pancreatic edema, acinar cell necrosis, and pancreas myeloperoxidase activity (an indicator of neutrophil infiltration). Lung injury was quantitated by evaluating lung microvascular permeability and lung myeloperoxidase activity.


RESULTS
In pancreatic tissue from control mice and cerulein-treated mice, the expression of both CD40 and CD40L was detected. Immunohistochemical analysis performed in isolated acini from wild-type pancreata showed that both CD40 and CD40L were expressed on the acinar cell surface. Interestingly, pancreatitis and pancreatitis-associated lung injury were markedly decreased in mice deficient in CD40L compared with wild-types.


CONCLUSIONS
These observations indicate that CD40L plays an important proinflammatory role in pancreatitis and pancreatitis-associated lung injury.
Frossard
J L
JL
Division of Gastroenterology, Geneva University Hospitals, Rue Micheli du Crest, 1211 Geneva 14, Switzerland. jean-louis.frossard@hcuge.ch
Kwak
B
B
Chanson
M
M
Morel
P
P
Hadengue
A
A
Mach
F
F
D000208:Acute Disease; D000681:Amylases / Q000097:blood / Q000378:metabolism; D000818:Animals; D023201:CD40 Ligand / Q000235:genetics / Q000502:physiology*; D002108:Ceruletide / Q000633:toxicity*; D008171:Lung Diseases / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D008297:Male; D051379:Mice; D010195:Pancreatitis / Q000139:chemically induced* / Q000150:complications / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000302:isolation & purification / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D002108:Ceruletide; D000681:Amylases