title: The MUC5AC glycoprotein is the primary receptor for Helicobacter pylori in the human stomach.
abstract: OBJECTIVE
  Helicobacter pylori shows a characteristic tropism for the mucus-producing gastric epithelium. In infected patients, H. pylori colocalizes in situ with the gastric secretory mucin MUC5AC. The carbohydrate blood-group antigen Lewis B (LeB) was deemed responsible for the adherence of H. pylori to the gastric surface epithelium. We sought to determine if MUC5AC is the carrier of LeB, and thus if MUC5AC is the underlying gene product functioning as the main receptor for H. pylori in the stomach.
  
  
  METHODS
  We studied three types of human tissue producing MUC5AC: Barrett's esophagus (BE), normal gastric tissue, and gastric metaplasia of the duodenum (GMD). Tissue sections were immuno-fluorescently stained for MUC5AC or LeB, and subsequently incubated with one of three strains of Texas red-labeled H. pylori, one of which was unable to bind to LeB. We determined the colocalization of MUC5AC or LeB with adherent H. pylori.
  
  
  RESULTS
  The binding patterns for the two LeB-binding strains to all tissues were similar, whereas the strain unable to bind to LeB did not bind to any of the tissues. In normal gastric tissue, the LeB-binding strains always bound to MUC5AC- and LeB-positive epithelial cells. In four nonsecretor patients, colocalization of the LeB-binding strains was found to MUC5AC-positive gastric epithelial cells. In BE, the LeB-binding H. pylori strains colocalized very specifically to MUC5AC-positive cells. MUC5AC-producing cells in GMD contained LeB. Yet, LeB-binding H. pylori not only colocalized to MUC5AC or LeB present in GMD, but also bound to the LeB-positive brush border of normal duodenal epithelium.
  
  
  CONCLUSIONS
  Mucin MUC5AC is the most important carrier of the LeB carbohydrate structure in normal gastric tissue and forms the major receptor for H. pylori.
authors.affiliation: Laboratory of Pediatrics, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Jeroen H B
authors.initials: JH
authors.lastname: Van de Bovenkamp
authors.forename: Jafar
authors.initials: J
authors.lastname: Mahdavi
authors.forename: Anita M
authors.initials: AM
authors.lastname: Korteland-Van Male
authors.forename: Hans A
authors.initials: HA
authors.lastname: Büller
authors.forename: Alexandra W C
authors.initials: AW
authors.lastname: Einerhand
authors.forename: Thomas
authors.initials: T
authors.lastname: Borén
authors.forename: Jan
authors.initials: J
authors.lastname: Dekker
mesh_terms: D018829:Adhesins, Bacterial; D001422:Bacterial Adhesion; D001471:Barrett Esophagus / Q000378:metabolism / Q000382:microbiology; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000737:chemistry; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism / Q000382:microbiology; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D004947:Esophagus / Q000378:metabolism / Q000382:microbiology; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology*; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D016480:Helicobacter pylori / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology; D007983:Lewis Blood Group Antigens / Q000737:chemistry / Q000378:metabolism; D008679:Metaplasia; D055271:Mucin 5AC; D009077:Mucins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; C400429:BabA protein, Helicobacter pylori; D002241:Carbohydrates; D002352:Carrier Proteins; D006023:Glycoproteins; D007983:Lewis Blood Group Antigens; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins