5-lipoxygenase knockout mice exhibit a resistance to acute pancreatitis induced by cerulein.
Here we compare the degree of pancreatitis caused by cerulein in mice lacking 5-lipoxygenase (5-LO) and in the corresponding wild-type mice. Intraperitoneal injection of cerulein in mice resulted in severe, acute pancreatitis characterized by oedema, neutrophil infiltration and necrosis and elevated serum levels of amylase and lipase. Infiltration of pancreatic and lung tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for intracellular adhesion molecule-1 (ICAM-1), P-selectin and E-selectin in the pancreas and lung of cerulein-treated mice. In contrast, the degree of (1) pancreatic inflammation and tissue injury (histological score), (2) up-regulation/expression of P-selectin, E-selectin and ICAM-1, and (3) neutrophil infiltration was markedly reduced in pancreatic and lung tissue obtained from cerulein-treated 5-LO-deficient mice. These findings support the view that 5-LO plays an important, pro-inflammatory role in the acute pancreatitis caused by cerulein in mice.
Cuzzocrea
Salvatore
S
Department of Clinical and Experimental Medicine and Pharmacology, Policlinico Universitario, Messina, Italy. salvator@unime.it
Rossi
Antonietta
A
Serraino
Ivana
I
Di Paola
Rosanna
R
Dugo
Laura
L
Genovese
Tiziana
T
Britti
Domenico
D
Sciarra
Giuseppe
G
De Sarro
Angelina
A
Caputi
Achille P
AP
Sautebin
Lidia
L
D000208:Acute Disease; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002108:Ceruletide; D019040:E-Selectin / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015227:Lipid Peroxidation; D008107:Liver Diseases / Q000201:enzymology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D019007:P-Selectin / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D012128:Respiratory Distress Syndrome / Q000201:enzymology / Q000473:pathology
D019040:E-Selectin; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D002108:Ceruletide; D001094:Arachidonate 5-Lipoxygenase