Role of macrophage inflammatory peptide-2 in cerulein-induced acute pancreatitis and pancreatitis-associated lung injury.
Acute pancreatitis is an inflammatory process of variable severity, and leukocytes are thought to play a key role in the development of pancreatitis and pancreatitis-associated lung injury. The effects of mediators released by these inflammatory cells may induce tissue damage. The aim of our study was to evaluate the role of the chemokine, macrophage inflammatory protein-2 (MIP-2), in the pathogenesis of cerulein-induced pancreatitis and pancreatitis-associated lung injury. The severity of pancreatitis was measured by serum amylase, pancreatic edema, acinar cell necrosis, and myeloperoxidase activity. Lung injury was quantitated by evaluating lung microvascular permeability and lung myeloperoxidase activity. To determine the role of MIP-2 in the pathophysiology of the disease, anti-MIP-2 antibody was administered either 1 hour before or 2 hours after the start of cerulein administration. MIP-2 concentrations increased in serum, pancreas, and lung tissues in mice treated with cerulein. Anti-MIP-2 antibody administrated either before or after cerulein partially protected against pancreas and lung injury. These results show that MIP-2 plays a key role in the pathophysiology of acute pancreatitis and that MIP-2 blockade may improve the outcome of the disease.
Pastor
Catherine M
CM
Division of Gastroenterology and Hepatology, Geneva University Hospital, Geneva, Switzerland.
Rubbia-Brandt
Laura
L
Hadengue
Antoine
A
Jordan
Martha
M
Morel
Philippe
P
Frossard
Jean Louis
JL
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D002108:Ceruletide / Q000008:administration & dosage / Q000633:toxicity; D054426:Chemokine CXCL2; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000633:toxicity; D007274:Injections, Intraperitoneal; D008171:Lung Diseases / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015846:Monokines / Q000502:physiology*; D009336:Necrosis; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D009195:Peroxidase / Q000097:blood
D054426:Chemokine CXCL2; D005765:Gastrointestinal Agents; D015846:Monokines; D002108:Ceruletide; D009195:Peroxidase; D000681:Amylases