The role of neutrophils and platelet-activating factor in mediating experimental pancreatitis.
OBJECTIVE
Pancreatitis is characterized by inflammation and death of acinar cells. Death can occur by either necrosis or apoptosis. The initial injury may cause expression of cytokines that mediate activation and infiltration of neutrophils. The aim of this study was to assess the effect of neutrophils and platelet-activating factor (PAF) in cell death responses.


METHODS
The effects of neutrophil depletion with antineutrophil serum (ANS) and a PAF antagonist (BN52021) were measured in the cerulein model of pancreatitis. Rats received a 6-hour intravenous infusion of cerulein either alone or after treatment with ANS, BN52021, or both.


RESULTS
Cerulein-induced pancreatitis was characterized by neutrophilic infiltration, vacuolization of acinar cells, and foci of necrosis. Treatment with ANS and BN52021 prevented the inflammatory response caused by cerulein and decreased the cell damage. Treatment with ANS increased apoptosis in cerulein-infused animals. When BN52021 was added, apoptosis was abolished. The measurement of PAF in pancreatic tissue showed a ninefold increase with cerulein treatment alone and a 14-fold increase in cerulein-infused, neutrophil-depleted animals.


CONCLUSIONS
The results indicate that cerulein stimulates pancreatic production of PAF. PAF mediates both apoptosis and neutrophil chemotaxis in the pancreas. Neutrophils in turn may convert acinar cells undergoing apoptosis into necrotic cells.
Sandoval
D
D
Department of Medicine, Veterans Affairs Medical Center, University of California San Diego, La Jolla, USA.
Gukovskaya
A
A
Reavey
P
P
Gukovsky
S
S
Sisk
A
A
Braquet
P
P
Pandol
S J
SJ
Poucell-Hatton
S
S
D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D002108:Ceruletide; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology; D008049:Lipase / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D010195:Pancreatitis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D010972:Platelet Activating Factor / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D002108:Ceruletide; C045856:ginkgolide B; D008049:Lipase; D000681:Amylases