Influence of platelet activating factor on expression of adhesion molecules in experimental pancreatitis

To determine whether Platelet activating factor (PAF) has a regulation role in the expression of adhesion molecules and accumulation of neutrophils in a murine model of acute pancreatitis.

One hundred twenty-eight Kunming mice were divided into four groups. Group 1 received 0.1 ml saline s.c. every hour for three hours (sham). Group 2 received cerulein (50 microg/kg dose s.c.) every hour for three hours. Group 3 received AP and additional challenge of PAF (50 mg/kg in absolute ethanol) (AP/PAF). Group 4 received AP, plus therapeutic treatment with GAB (25 mg dose i.p.) immediately after the first challenge of cerulein (AP/GAB). Animals were sacrificed at 12 h after the first challenge of saline or cerulein. Adhesion molecules of pancreas were semi-quantified by SP methods. Standard assays were performed for serum amylase and myeloperoxidase activity (MPO) of pancreas. Histology of pancreas was scored in a blind manner. Water content of pancreas was also measured at the same time.

Control pancreata showed negligible adhesion molecule expression and neutrophil accumulation. There were evident adhesion molecules expression and neutrophil accumulation in AP and AP/PAF compared with sham (P<0.05). AP/GAB had a lower level of adhesion molecules, neutrophils, and water content versus AP and AP/PAF (P<0.05). Histology showed a trend toward improvement in AP/GAB, but did not reach statistical significance.

PAF can induce the expression of adhesion molecules that mediate neutrophil accumulation. The PAF antagonist reduces the expression of adhesion molecules and the severity of inflammation when given immediately after the induction of mild AP in mice. These results suggest that PAF antagonism may be useful in the treatment of mild pancreatitis after its clinical onset.