Pancreatic Cationic Elastase in Porcine Experimental Pancreatitis

Abstract

A radioimmunoassay for porcine, cationic, pancreatic elastase (irPE) is described. Normal porcine serum contains only small amounts of irPE (<3 µg/l). IrPE in serum and peritoneal exudate from 6 pigs with experimental pancreatitis was found mainly in a molecular form corresponding to free pro-enzyme. The presence of α₁-, α₂-macroglobulin-bound elastase-like enzymatic activity in the peritoneal exudates from pigs with pancreatitis, however, indicates that the proteinase is to some extent released as the active enzyme. In some pigs with pancreatitis, the elastase-like activity against Succ(Ala) in the peritoneal exudates increased during the experiment, arguing for a progressive activation of pro-elastase. Free proteolytic activity was not observed in any of the peritoneal exudates. This low degree of activation of elastase and the fact that the elastase inhibiting capacity is substantially larger than the trypsin inhibiting capacity in serum and biological fluids, leads us to the conclusion that active elastase is not a factor of principal importance in the pathogenesis of proteinase inhibitor consumption and tissue damage in our experimental pancreatitis model.

Studies on the Release of Tissue Kallikrein in Experimental Pancreatitis in the Pig

“…This usually results in a dose-response curve that is nonparallel to the standard curve, which these authors also re ported [21]. The low recovery of active tissue kallikrein when added to plasma and perito neal fluid in this study, and previously also reported in the rat and human [22,23], indi cates that such complex formation takes place, even though it has been reported that porcine tissue kallikrein does not bind to alpha-macroglobulins [24], However, the larg er recovery of active tissue kallikrein from normal peritoneal fluid compared with plas ma supports the theory of alpha-macroglobulin complexes masking the immunoreactivity, as the level of alpha-macroglobulins in normal porcine peritoneal fluid is only about 10% of that in plasma [11,13]. Furthermore the a Fig.…”

“…Another possible explana tion for the low recovery is the loss of immunoreactivity of the active tissue kallikrein due to enzymatic proteolysis of the kallikrein mol ecule by enzymes present in plasma [26,27], Bile-induced, experimental pancreatitis is thought to resemble bilestone-associated pan creatitis in man, although some authors con- sider that the model has some shortcomings [28]. Our experimental models are well-stan dardized models [12] and have been used by us in several earlier studies [11,13]. The addi tion of trypsin to the injected bile results in a more severe pancreatitis and enhanced mor tality.…”

“…Pancreatitis was induced in group A by injection of 30 ml of a solution of 15% (w/v) sodium taurocholate and 30% (v/v) bile (from the pig) into the pancreatic duct over 30 s [ 11,12] and in group B by injection of a solution of 20 ml 15 % (w/v) sodium taurocholate and 0.1% (w/v) porcine trypsin into the pancreatic duct over 1 min with an automatic syringe pump [12,13], The abdomen was closed. The experiment was continued for 24 h. or less if the pig died earlier.…”