Digestive and Liver Disease 37 (2005) 232–239 Alimentary Tract Increased phospholipase activity in Helicobacter pylori strains isolated from patients with gastric carcinoma P. Lusini a,1 , N. Figura b,1 , M. Valassina a , F. Roviello c , C. Vindigni d , L. Trabalzini a , R. Nuti b , C. Lenzi b , C. Gonnelli b , M. Nardi b , P. Martelli a , A. Santucci a,∗ a Department of Molecular Biology, University of Siena, 53100 Siena, Italy b Department of Internal Medicine, University of Siena, 53100 Siena, Italy c Surgical Unit, University of Siena, 53100 Siena, Italy d Oncology Department, University of Siena, 53100 Siena, Italy Received 16 July 2004; accepted 11 November 2004 Available online 6 January 2005 Abstract Purpose. Phospholipase activity, one of Helicobacter pylori pathogenicity factors, has not been investigated enough, so far, although it may induce a remarkable damage to the gastric mucosa. In the present work, we have compared the whole phospholipase activity of H. pylori strains isolated from patients with gastric carcinoma with that of strains isolated from dyspeptic patients without gastric carcinoma. Methods. We measured the phospholipase activity of one distinct H. pylori colony isolated from each of 10 patients with gastric carcinoma and 10 controls, dyspeptic patients without endoscopic and histological signs of gastric carcinoma. We also determined the phospholipase activity of 20 additional strains isolated from different areas of neoplastic and non-neoplastic tissue of two patients with gastric carcinoma, the cagA and vacA positive G27 and 328 wild strains and their respective vacA and cagA negative isogenic mutants. The whole phospholipase activity of strains was determined by measuring the release of 14 C-labeled palmitic acid from the radioactive l-3-phosphatidylcholine, 1,2- di[1- 14 C]palmiloyl substrate; results were expressed in pmol of palmitic acid per mg of protein. Results. H. pylori strains isolated from patients with gastric carcinoma had levels of phospholipase activity significantly higher than those of strains isolated from controls (99.37 [S.D. 40.45] versus 34.46 [S.D. 16.46], P < 0.001). In patients with gastric carcinoma, the mean phospholipase activity of strains isolated from neoplastic tissue was similar to that of strains isolated from non-neoplastic tissues (123.02 [S.D. 44.36] and 115.77 [S.D. 81.48], respectively. Interruption of cagA gene caused a ca. 20% reduction of phospholipase activity (36.38 versus 45.22 of the wild strain); that of vacA caused no reduction of phospholipase activity (26.53 and 25.37 of the wild strain). Conclusions. The infection by H. pylori strains that produce high levels of phospholipase may increase the risk of developing gastric carcinoma. We hypothesise that indirect products of phospholipase activity, such as prostaglandins, leukotrienes and lysophospholipids, may mediate carcinogenesis. © 2004 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: cagA; Gastric carcinoma; H. pylori; Phospholipase; vacA 1. Introduction H. pylori infection is a main cause of chronic gastritis and an important determinant of peptic ulcer, gastric carcinoma ∗ Corresponding author. Tel.: +39 0577 234958; fax: +39 0577 234903. E-mail address: santucci@unisi.it (A. Santucci). 1 These authors contributed equally to the work. (GC) and MALT lymphoma [1]. Both the virulence factors produced by H. pylori [2] and the concomitant host inflamma- tory response contribute to injure the gastric mucosa [3–5]. The immune response to the infection involves initially neu- trophils, lymphocytes, eosinophils and monocytes [5] and is both local, IgA-mediated, and systemic, IgG-mediated [6]. The bacterial products and components continue to stimu- late the inflammatory response and may therefore contribute 1590-8658/$30 © 2004 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dld.2004.11.004