Intracellular vacuolization caused by the urease of Helicobacter pylori

Tissue culture cells were exposed to supernatants of Helicobacter pylori for 24 h at 37 degrees C in the presence of various quantities of urea. In the normal human stomach the concentration of urea is less than or equal to 4 mmol/l, and in the presence of this low concentration up to 10% of Vero cells showed intracellular vacuolization. In the presence of 7.5 mmol/l urea, 25% of the cells showed vacuolization. With 30 mmol/l urea, the final pH was 7.6, indicating that vacuolization was not due to change of pH. The first report of vacuolization of tissue culture cells by H. pylori was in a system without added urea but with concentrated bacterial supernatant; 30% of H. pylori strains demonstrated a cytotoxic effect. In those experiments fetal calf serum was used; it contains 6 mmol/l urea but was used at a concentration of 10%. A urease inhibitor, acetohydroxamic acid, caused a 75% drop in the number of cells showing vacuolization, and ammonia caused vacuolization. Thus the urea of H. pylori probably causes this vacuolization.