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

Abstract

The activation of the kallikrein-kinin system is thought to be one of the pathophysiological factors in acute pancreatitis. A radioimmunoassay for porcine, pancreatic tissue kallikrein was developed and used to measure levels in normal plasma and peritoneal fluid and in experimental, bile-induced (group A) and bile trypsin-induced (group B) acute pancreatitis in the pig. Normal porcine plasma and peritoneal fluid contained about 2.17 +/- 0.11 and 1.91 +/- 0.19 microgram/l (SEM) tissue kallikrein, respectively. In experimental, acute pancreatitis there was a rapid rise in the plasma level of tissue kallikrein, followed by a slow increase to a final value of about 150% of the normal plasma level in both groups. In the peritoneal exudate a large increase (200-fold in group A and 2,000-fold in group B) in tissue kallikrein was seen, with a maximum within about 1/3 of the survival time, followed by a slow decrease until death in group B. In group A a smaller second peak was seen at about 2/3 of the survival time. Gelfiltration of peritoneal exudates showed complexes with alpha 1-, alpha 2-macroglobulin (alpha 1 alpha 2-M), and alpha 1-proteinase inhibitor (alpha 1-PI) and a large portion of free tissue kallikrein. The complexes with alpha 1 alpha 2-M and the free tissue kallikrein were found to be enzymatically active when tested on chromogenic tripeptide substrate. The presence of large amounts of free and active tissue kallikrein in the peritoneal exudate leads us to the conclusion that tissue kallikrein may be a major cause of local release of kinins in acute pancreatitis.