Digestive Diseases and Sciences, l/ol. 40, No. 11 (November 1995), pp. 2473-2476 Influence of Helicobacter pylori on Tryptase and Cathepsin D in Peptic Ulcer M. PLEBANI, MD, D. BASSO, MD, M. RUGGE, MD, F. VIANELLO, MD, and F. DI MARIO, MD We here ascertain whether tryptase (a serine endoprotease released by mast cells) and cathepsin D (CD, a lysosomal hydrolase that seems able to derange the extracellular matrix) play a part in peptic ulcer disease and whether they are linked to Helicobacter pylori (Hp) infection. We studied 13 controls, 25 patients with gastric ulcer, 47 with duodenal ulcer, and 11 with duodenitis. Tryptase and CD were measured in mucosal biopsies (body and antrum of the stomach and duodenum) using IRMA methods. Hp infection was histologically evaluated (Giemsa). Tryptase and CD levels were higher (25%) in patients with active peptic ulcer, whether gastric or duodenal. In Hp-positive patients the CD mucosal content was higher while tryptase mucosal levels were lower than in Hp-negative patients. Tryptase was correlated with gastrin content. CD seems to be mainly related to the phlogistic reaction of the mucosa to Hp infection; tryptase may reflect an indirect link between Hp infection, gastrin release, and the function of mast cells. KEY WORDS: peptic ulcer, tryptase, cathepsin D, Helicobacter pylori. The role of mast cells in the pathogenesis of gastrodu- odenal damage has been experimentally demon- strated (1). However, the molecular mechanism in- volved is not yet completely understood. Mast cells contain and can release several vasoactive substances, histamine, and proteolytic enzymes, including tryptase, all of which can damage the gastroduodenal mucosa (2-4). Other exogenous and endogenous factors are in- volved in the pathogenesis of gastroduodenal dam- age. Although it is known that Helicobacter pylori (Hp) infection causes atrophic chronic gastritis and is associated with duodenal ulcer (5-8), it is not known whether this microorganism damages the gastroduo- denal mucosa directly or indirectly. As regards the Manuscript received February 22, 1994; revised manuscript re- ceived July 26, 1994; accepted May 23, 1995. From the Istituto di Medicina di Laboratorio and Cattedra di Gastroenterologia, University of Padova; Cattedra di Istochimica ed Immunoistochimica Patologica, USL i9, University of Padova, Italy. Address for reprint requests: Dr. Mario Plebani, Dipartimento di Medicina di Laboratorio, c/o Laboratorio Centrate, Via Giustiniani 2, 35128 Padova, Italy. first aspect, Hp has been found to produce at least one cytotoxin. Regarding the second, it has been demonstrated that Hp causes an enhanced gastrin release due to its inhibitory effect on somatostatin release, and this leads to an enhanced gastric acid secretion (9). Furthermore, Hp infection causes gas- tric inflammation which, via the release of vasoactive substances and enzymes, might contribute in damag- ing the mucosa. Among other lysosomal enzymes, cathepsin D (CD), which is able to digest the extra- cellular matrix, can be released in inflamed tissues (10-13). In peptic ulcer Hp infection, mast cell prod- ucts and lysosomal enzymes may be involved and may interact with each other. The aims of this study were to: (1) verify whether tryptase is present in gastric mucosal mast cells and, if so, to ascertain whether there is a relation- ship between mucosal mast cell content and tryptase levels; (2) evaluate the behavior of tryptase and CD in patients with peptic ulcer; and (3) as- certain whether both enzymes are associated with the Hp infection. Digestive Diseases and Sciences, Vol. 40, No. 11 (November 1995) 11163o2116/95/1 I00-2473507.50/0 © 1995 Plenum Publishing Corporation 2473