Purification and Radioimmunoassay of Psti

We studied the distribution of pancreatic secretory trypsin inhibitor (PSTI) in the epithelia of the gastrointestinal tract and determined whether PSTI is secreted into gastric juice. PSTI was measured by a specific radioimmunoassay in biopsy specimens taken from the upper (n=8) and lower (n=7) gastrointestinal tract of patients with normal endoscopies. PSTI was present in the stomach, small intestine, and colon. Concentrations (1ig/g protein) were highest in the stomach, and significantly higher in the antrum (1240, 670-1700, median and range) than in the gastric body (370, 350-570) (p<001). Concentrations were similar in the duodenum (180, 80-210) and colon (160, 130-360). PSTI determined by immunohistochemistry was present in mucus secreting gastric foveolar cells, duodenal Paneth cells, and colonic non mucus cells. PSTI was present in gastric juice. The median (range) concentration ofPSTI in basal gastric juice from 13 patients with duodenal ulcers was 9 (3-21) .tg/l and did not change during stimulation with pentagastrin. The rate of secretion, however, did increase significantly (p<0c05) from 1430 (180-2810) ng/h to 4500 (1250-12 770) ng/h during pentagastrin stimulation. PSTI was labile in acid pepsin but stable in the neutral conditions present in the mucus layer. The presence of pancreatic secretory trypsin inhibitor throughout the gut and its secretion into the lumen suggests a hitherto unrecognised mechanism protecting gastrointestinal epithelia against luminal proteases. Gastroenterology Unit, Department ofMedicine, Royal Postgraduate Medical School, Du Cane Road, London W12 ONN T C Freeman R J Playford C Quinn K Beardshall J Calam Biotechnology L Poulter and Bioscience, ICI Phannaceuticals, Macclesfield, Cheshire J Young Correspondence to: Dr John Calam. Accepted for publication 16 January 1990 Pancreatic secretory trypsin inhibitor (PSTI) is a small protein containing 56 amino acid residues which was originally isolated from bovine pancreas,' and human PSTI has now been purified24 and cloned.5 PSTI is thought to protect the pancreas from prematurely activated proteases but the recent demonstration of PSTI-like immunoreactivity (PSTI-LI) in other regions of the gut"8 and its isolation from the human stomach,9 suggests that PSTI may protect the whole gastrointestinal tract. The present study was undertaken to determine epithelial concentrations of PSTI using biopsy specimens obtained from the stomach, small intestine, and colon and to study the cellular distribution of PSTI-LI. We also analysed gastric juice to determine whether PSTI is secreted into the lumen.