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

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.