Effect of persistent and transient H. pylori infection of H,K-ATPase and sialylated lewis antigens expression: Role of the host lewis gastric phenotype

Abstract

Persistent H pyIo~i infection causes peptic ulcer disease (PUD) or gastric cancer in a subset of inf~:cted su/~lects rha Lewis (Lea antigens expressed on epithelial surfaces are receptors fur pathogenic microorgainsm_s, and undergo changes during miection and pre-malignant n~nsfbrmatton t:{, py'lor~ uses two dill}rent adhesins that bind the Le '~ and sialyl keantigens, respectively In addition, tbe association of LeU/Seeretor status and PUD is controversial. The aim of this study was to determine the relation between fhe l_e antigens, H. pylon infection and H,K AI'Pase expression pnor, and for 10 montbs tbllowmg, H, pylori inoculation Gastric corpus arid antral biopsies were harvested at endoscopy in 9 rhesus monkeys, and expression of Le antigens and H,K-ATPase was detennined using innnunohistochemistry and digital immunoquantitatim'~ In vitro adherence of Leand sialyl-Le~-binding strains was determined as leported (Scie ~ce, 2002; 297:573-578) 6 Animals were Le~'-positive (Le § i,e, positive secretor phenotype) and 3 were Ld-negative (Le ) Basally, sialyl-Le and H,K-ATPase expression was stgnihcandy greater in L e ' than in le ~' animals (14 • 4% ,Is 4 • 3% and 37 • 3% vs 26 • 4 % respectively; p than m Le* animals, and H,K-?dPaae expression was less in in L& than in Ld '+ animals (P <0,05) In Le b animaIs, H,K-ATFase expression was directly correlated with H. pylori density, and inversely correlated with sialyl-Le expression (p <0,05). In vitru adherence of a Le~'-binding strain was sigmflcantly higher in I.e b' than in Le ~ animals and it decreased at 1 -week post inoculation (p <005) . In contrast, adherence of a sialyl-Le* binding strain was similar in Ld '+ and Le animals bethre inoculation, and it increased significantly post inoculation, with the le t animals bmding twice as much as the Le b+ animals. The data indicate that acute and persistent H pyIor: inlimrion reduces time-dependent changes in expression of sia/yl-le antigens on gastric epithelial ceils and within tbe larnina pmpria, and that la ,b positive and negative subients differ markedly in terms of post-inoculation bacterial load and mueosal response Thns, the Lewis system may play a role in determining the boa[ outcome of persistent infection, ie, no disease PUD, or gastric cancer,