Tissue kallikrein: pathophysiological role in acute pancreatitis

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Tissue kallikrein releases pharmacollogically highly active kinins from kininogen. Many other enzymes may also release kinins. The aim of the study was to clarify the pathophysiological role of tissue kallikrein in acute pancreatitis.

Two sensitive and specific radioimmunoassays for porcine and human tissue kallikrein were developed. A large release of tissue kallikrein from the pancreatic gland into the peritoneal exudate was found in both experimental acute pancreatitis in pigs and in clinical acute pancreatitis. Tissue kallikrein may be a major cause of locally released kinins in acute pancreatitis. Pigs seem to lack the specific tissue kallikrein inhibitor kallistatin found in humans and instead alpha1alpha2-macroglobulins were found to be the major inhibitors of tissue kallikrein. Inhibition of released tissue kallikrein in acute pancreatitis in pigs appears to be insufficient both locally and in plasma. In humans, tissue kallikrein was bound to kallistatin both when tissue kallikrein was intravenously injected and when released in acute pancreatitis. The binding of tissue kallikrein to the plasma protease inhibitors was found to be biologically slow, even if faster in vivo than in vitro. A small fraction of intravenously injected tissue kallikrein in both humans and pigs was found unbound and this may have physiological or pathophysiological effects. No unbound tissue kallikrein was found in clinical acute pancreatitis. Low kallistatin levels in peritoneal exudate and plasma may act as an early marker of severity or pancreatic necrosis in acute pancreatitis. No uptake of intact tissue kallikrein from the gut into the circulation could be demonstrated.

Details

Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Clinical Medicine

Keywords

  • acute pancreatitis, aprotinin, alpha-macroglobulin, alpha1-proteinase inhibitor, turn over, kinin B2 receptor, kallidin, bradykinin, Tissue kallikrein, kallistatin, Surgery, orthopaedics, traumatology, Kirurgi, ortopedi, traumatologi
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
  • [unknown], [unknown], Supervisor, External person
Award date2001 Oct 5
Publisher
  • Department of Surgical Pathophysiology, Malmö University Hospital, SE-205 02 Malmö, Sweden
Print ISBNs91-628-4950-6
Publication statusPublished - 2001
Publication categoryResearch

Bibliographic note

Defence details Date: 2001-10-05 Time: 09:15 Place: Department of Surgery, Malmö University Hospital, Entrance 42 External reviewer(s) Name: Stenman, Ulf-Håkan Title: Professor Affiliation: Department of Clinical Chemistry, Helsingfors University Hospital --- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Emergency medicine/Medicine/Surgery (013240200), Campus Helsingborg - Clinical Sciences (013230013)