The effects of neutrophil depletion on a completely noninvasive model of acute pancreatitis-associated lung injury.
CONCLUSIONS
A completely noninvasive animal model of acute pancreatitis-associated lung injury was used to show that neutrophils, activated by pancreatitis, play a key role in mediating pancreatitis-associated lung injury.


BACKGROUND
Significant pulmonary complications have been known to occur in over 50% of patients with severe acute pancreatitis. Recent studies using a variety of animal models of pancreatitis have suggested that neutrophil activation may play an important role in mediating lung injury. However, in these models, the interpretation of the results is complicated because surgical manipulations alone could have resulted in the activation of neutrophils.


METHODS
Young female mice were fed a choline deficient ethionine (CDE) supplemented diet. The severity of pancreatitis was evaluated by measuring hyperamylasemia, acinar cell necrosis, and pancreatic myeloperoxidase activity. Lung injury was quantified by measuring lung microvascular permeability and lung myeloperoxidase activity. To evaluate the role of neutrophils in CDE diet-induced pancreatitis-associated lung injury, animals were pretreated with antineutrophil serum.


RESULTS
Mice fed the CDE diet develop pancreatitis-associated lung injury. Pretreatment of mice with antineutrophil serum results in marked depletion of circulating neutrophils. Under these conditions, the severity of pancreatitis is reduced and lung injury is completely prevented.
Bhatia
M
M
Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Saluja
A K
AK
Hofbauer
B
B
Lee
H S
HS
Frossard
J L
JL
Steer
M L
ML
D000208:Acute Disease; D000818:Animals; D002794:Choline / Q000008:administration & dosage; D004032:Diet; D005001:Ethionine / Q000494:pharmacology; D005260:Female; D007116:Immunization, Passive; D007958:Leukocyte Count; D008171:Lung Diseases / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D010195:Pancreatitis / Q000150:complications* / Q000201:enzymology / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism
D009195:Peroxidase; D002794:Choline; D005001:Ethionine