1999 Abstract: 2153 SERUM CHANGES INDUCED BY TRYPSIN DURING ACUTE PANCREATITIS RESULT IN NEUTROPHIL ACTIVATION AND REMOTE ORGAN INJURY
Abstracts
|
Leukocytes have been shown to be involved in the development of pancreatic and pulmonary injury in acute pancreatitis, but the mechanisms initiating their activation are poorly understood. We investigated whether serum changes induced by trypsin can cause neutrophil activation and subsequent tissue injury in an animal model of pancreatitis. Methods: Serum was collected from inbred rats after induction of either mild edematous (i.v. cerulein) or severe necrotizing pancreatitis (intraductal glycodeoxycholic acid + i.v. cerulein). Normal rat serum was similarly collected and incubated with different concentrations of trypsin (10-10, 10-8, 10-6, 10-4 mol/L). Pancreatitis or trypsinized serum was incubated in vitro with leukocytes separated from blood of healthy animals. CD11b expression, an adhesion molecule that is upregulated on the surface of activated neutrophils, was measured quantitatively by flow-cytometry using a monoclonal antibody. To assess the consequences of these circumstances in vivo, trypsin-incubated serum was infused into rats for 6 hours, and pancreatic and pulmonary injury were quantitated by measurement of edema (wet-to-dry weight ratio) and leukocyte infiltration (myeloperoxidase activity). Results: CD11b expression on neutrophils incubated with serum from animals with pancreatitis was increased compared to controls (p<0.04). CD11b expression did not differ between neutrophils incubated with serum from mild or severe pancreatitis. Neutrophils incubated with trypsinized serum showed increased expression of CD11b compared to controls. Levels of CD11b expression increased with increasing trypsin concentrations (p<0.001). Pancreata and lungs of animals exposed to trypsinized serum showed significant elevations in edema (p<0.01) and myeloperoxidase activity (p<0.03). Pulmonary injury was similar to or worse than that produced by severe pancreatitis. Conclusion: Pancreatitis causes changes in serum that result in neutrophil activation. This phenomenon can be replicated by treatment of resting neutrophils in vitro with trypsinized serum. Intravascular activation of neutrophils by pancreatic proteases released during acute pancreatitis may contribute to both local pancreatic and remote organ injury. Copyright 1996 - 1999, SSAT, Inc. |