Abstract
Helicobacter pylori, a Gram-negative gastric bacterium, secretes VacA, a cytotoxin that causes vacuolar degeneration of susceptible cells. Velocity sedimentation analysis showed that treatment of VacA at alkaline pH led to disassembly of VacA oligomers, an observation reported previously for acid-treated VacA. Exposure of VacA to acid or alkali increased its binding to AZ-521 cells, as shown by indirect immunofluorescence and flow cytometry. Moreover, immunoprecipitates with polyclonal antibodies against VacA from AZ-521 cells previously exposed to acid- or alkali-treated VacA had a 250-kDa glycoprotein containing galactose-beta(1-3)-N-acetylgalactosamine and galactose-beta(1-4)-N-acetylglucosamine. p250, purified by chromatography on peanut agglutinin affinity and Superose 6 columns, contained N-terminal and internal amino acid sequences of YRQQRKLVEEIGWSYT and LIIQDHILEATQDDY, respectively. These sequences are identical to those of a receptor protein-tyrosine phosphatase (RPTPbeta/PTPzeta); in agreement, p250 reacted with anti-human RPTPbeta monoclonal antibody. Immunoprecipitation with anti-human RPTPbeta antibody of solubilized membrane preparations previously incubated with VacA or heat-inactivated VacA demonstrated that RPTPbeta bound native, but not denatured, VacA. Acidic and alkaline treatments were associated with activation of VacA and increased binding to the cell surface RPTPbeta.
Highlights
Helicobacter pylori causes chronic, active gastritis and peptic ulcer disease and is a risk factor for gastric cancer [1]
H. pylori grows persistently in the mucus layer of gastric tissue by means of a potent urease which produces ammonia; this product plays a significant role in the neutralization of the acidic environment of the stomach [9] and allows the bacteria in vivo to adhere to the apical plasma membrane of surface epithelial cells in the pyloric antrum (10 –12)
It is probable that a non-acidic or alkaline environment is created by ammonia produced from urea secreted by gastric epithelial cells by action of H. pylori urease, even though the gastric juxtamucosal pH of patients infected with H. pylori is 5.7 [14]
Summary
Helicobacter pylori causes chronic, active gastritis and peptic ulcer disease and is a risk factor for gastric cancer [1]. Most H. pylori infections are asymptomatic, H. pylori type I secretes a potent vacuolating cytotoxin (VacA) and is associated with severe symptomatic gastritis. H. pylori grows persistently in the mucus layer of gastric tissue by means of a potent urease which produces ammonia; this product plays a significant role in the neutralization of the acidic environment of the stomach [9] and allows the bacteria in vivo to adhere to the apical plasma membrane of surface epithelial cells in the pyloric antrum (10 –12). It is probable that a non-acidic or alkaline environment is created by ammonia produced from urea secreted by gastric epithelial cells by action of H. pylori urease, even though the gastric juxtamucosal pH of patients infected with H. pylori is 5.7 [14]. Rapid vacuolation of AZ-521 cells incubated with acid- or alkali-treated VacA was associated with its enhanced binding to a 250-kDa surface glycoprotein, termed p250. Amino acid sequence data and immunological analysis showed that p250 is receptor protein-tyrosine phosphatase  (RPTP).
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