title: Antimicrobial host defense in the upper gastrointestinal tract.
abstract: BACKGROUND
  With the exception of fungi, microbial infections are rare in the oesophagus. Herein, we aimed to systematically assess the distribution and quantity of different antimicrobial host factors as well as, for the first time, functional mucosal antimicrobial activity in the upper gastrointestinal tract.
  
  
  METHODS
  We investigated biopsies from the healthy oesophagus, three different locations in the stomach and the duodenum in a total of 12 individuals. Using real-time PCR with external standards, we compared absolute expression of mRNA encoding antimicrobial peptides including defensins, cathelicidin, bactericidal/permeability-increasing protein, psoriasin, and elafin. In addition, we performed immunostaining for human-beta-defensin-1 (HBD1), elafin, and psoriasin. To test functional relevance, we assessed antimicrobial as well as antifungal activity of cationic extracts from biopsies against E. coli ATCC 25922 and a clinical isolate of Candida albicans.
  
  
  RESULTS
  In contrast to HBD1 which was similarly expressed in all tissues, inducible beta-defensins in the healthy oesophagus were much higher compared with the stomach and duodenum (for HBD2-4: P<0.01). In addition, the antiproteases elafin and psoriasin were also predominantly expressed in the oesophagus (P<0.005). In contrast, LL-37 and bactericidal/permeability-increasing protein were only marginally expressed. Cationic tissue extracts from both the oesophagus as well as the stomach showed potent antibacterial activity against E. coli. Consistent with susceptibility to Candida infection, the esophageal extracts exhibited a weaker activity against C. albicans (P=0.026).
  
  
  CONCLUSIONS
  Despite dominant expression of antimicrobial host peptides, oesophageal tissue shows a weakened potency to kill C. albicans. These data suggest an important role of yet unknown antimicrobial molecules.
authors.affiliation: Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hosaka
authors.forename: Maureen
authors.initials: M
authors.lastname: Koslowski
authors.forename: Sabine
authors.initials: S
authors.lastname: Nuding
authors.forename: Guoxing
authors.initials: G
authors.lastname: Wang
authors.forename: Miriam
authors.initials: M
authors.lastname: Schlee
authors.forename: Christian
authors.initials: C
authors.lastname: Schäfer
authors.forename: Katunori
authors.initials: K
authors.lastname: Saigenji
authors.forename: Eduard F
authors.initials: EF
authors.lastname: Stange
authors.forename: Jan
authors.initials: J
authors.lastname: Wehkamp
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002176:Candida albicans / Q000472:pathogenicity; D002352:Carrier Proteins / Q000378:metabolism; D054804:Cathelicidins; D023082:Defensins / Q000378:metabolism; D053492:Elafin / Q000378:metabolism; D004926:Escherichia coli / Q000472:pathogenicity; D004947:Esophagus / Q000378:metabolism / Q000382:microbiology; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D019879:Paneth Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; D013270:Stomach / Q000382:microbiology; D041742:Upper Gastrointestinal Tract / Q000378:metabolism* / Q000382:microbiology; D023084:alpha-Defensins / Q000378:metabolism; D023083:beta-Defensins / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; C466096:BPIFB2 protein, human; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D054804:Cathelicidins; D023082:Defensins; D053492:Elafin; C506806:PI3 protein, human; D012333:RNA, Messenger; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D023084:alpha-Defensins; D023083:beta-Defensins