Secretory Leukocyte Protease Inhibitor (SLPI) in the gastrointestinal tract in man.

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Secretory leukocyte protease inhibitor is a 11.7 kDa acid stable serine protease inhibitor. SLPI has been shown to be the dominant protease inhibitor in bronchial secretions and has been used in treatment of pulmonary emphysema. In ulcerative colitis faecal extracts has been shown to contain an abundance of free proteolytic activity, mainly leukocytic and pancreatic proteases. SLPI is a strong inhibitor of many of these proteases.

In this thesis, we demonstrated immunoreactive SLPI in goblet like cells in the large bowel and in the small intestine. SLPI was also found in Paneth cells in the small intestine as well as in colonic adenomas. Pepsin as well as gastric and duodenal juice was found to rapidly degrade SLPI in vitro. After instillation of radiolabelled SLPI in the duodenum, no intact SLPI was found in faeces. We found mRNA for SLPI in pancreatic tissue and using immunohistochemical methods, the cells of Langerhan were shown to contain SLPI. In patients with ulcerative colitis, plasma SLPI was shown to be elevated and also to be correlated to the severity of the disease. In addition plasma levels of Neutrophil Gelatinase Associated Lipocalin (NGAL) were elevated and could possibly be a useful indicator of remission in patients with ulcerative colitis. Finally, a quantitative method for culturing colonic mucosa using punch biopsies was developed. The possible effect of added agents on the colonic mucosa production of SLPI and other inflammatory mediators such as cytokines, can be studied using this method.

In conclusion, this thesis showed the presence of SLPI in Paneth cells in the small intestines and in goblet cells both in the small and large intestines. Colonic adenomas were shown to contain SLPI as well. SLPI was degraded by gastric and duodenal juice and also by pepsin. SLPI production in the pancreas was shown as well as the presence of SLPI in the Islets of Langerhan. SLPI was significantly correlated to severity in patients with ulcerative colitis. NGAL could possibly be useful as an indicator of remission in UC. A quantitative method of standardised in vitro culturing of colonic mucosa was developed. In accordance, actual release of SLPI from the mucosa was shown.

Details

Authors
  • Max Nyström
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Clinical Medicine

Keywords

  • Surgery, elastase inhibitors, human leukocyt proteases, Plasma protease inhibitors, NGAL, Ulcerative colitis, Antileukoprotease, IBD, traumatologi, ortopedi, traumatology, orthopaedics, Immunology, serology, transplantation, Immunologi, serologi, Kirurgi
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
  • [unknown], [unknown], Supervisor, External person
Award date2002 May 13
Publisher
  • Max Nyström Dept of Surgical pathophysiology, Malmö university hospital SE 295 02 Malmö Sweden,
Print ISBNs91-89625-11-0
Publication statusPublished - 2002
Publication categoryResearch

Bibliographic note

Defence details Date: 2002-05-13 Time: 10:15 Place: Kirurgens föreläsningssal ing 42 UMAS External reviewer(s) Name: Venge, Per Title: Professor Affiliation: [unknown] --- Article: Paper ILocalization of immunoreactive secretory leukocyte protease inhibitor (SLPI) in intestinal mucosa.Magnus Bergenfeldt, Max Nyström, Måns Bohe, Clas Lindström, Åsa Polling, Kjell Ohlsson.Journal of Gastroenterology 1996; 31:18-23. Article: Paper IIThe elimination of secretory leukocyte protease inhibitor (SLPI) from the gas-trointestinal tract in man.Max Nyström, Magnus Bergenfeldt, Kjell Ohlsson.Scandinavian Journal of Clinical and Laboratory Investigation. 1997; 57: 119-126. Article: Paper IIIProduction of secretory leukocyte protease inhibitor (SLPI) in human pancreatic β-cells.Max Nyström, Magnus Bergenfeldt, Irena Ljungkrantz, Åsa Lindeheim, Kjell OhlssonMediators of Inflammation. 1999; 8: 147-151. Article: Paper IVElevated levels of Secretory Leukocyte Protease Inhibitor (SLPI), Neutrophil Ge-latinase Associated Lipocalin (NGAL), TNF-α, and IL-1ra in Patients With Acute Ulcerative Colitis (UC).Max Nyström, Ulla Peterson Westin, Anders Borgström, Magnus Bergenfeldt and Kjell Ohlsson. (In manus) Article: Paper VSecretory leukocyte protease inhibitor in punch biopsies from human colonic mu-cosaMax Nyström, Ulla Peterson-Westin, Carina Linder, Kjell OhlssonMediators of Inflammation. 2001; 10; 269-272. 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)