title: Human alpha defensin 5 expression in the human kidney and urinary tract.
abstract: BACKGROUND
  The mechanisms that maintain sterility in the urinary tract are incompletely understood. Recent studies have implicated the importance of antimicrobial peptides (AMP) in protecting the urinary tract from infection. Here, we characterize the expression and relevance of the AMP human alpha-defensin 5 (HD5) in the human kidney and urinary tract in normal and infected subjects.
  
  
  RESULTS
  Using RNA isolated from human kidney, ureter, and bladder tissue, we performed quantitative real-time PCR to show that DEFA5, the gene encoding HD5, is constitutively expressed throughout the urinary tract. With pyelonephritis, DEFA5 expression significantly increased in the kidney. Using immunoblot analysis, HD5 production also increased with pyelonephritis. Immunostaining localized HD5 to the urothelium of the bladder and ureter. In the kidney, HD5 was primarily produced in the distal nephron and collecting tubules. Using immunoblot and ELISA assays, HD5 was not routinely detected in non-infected human urine samples while mean urinary HD5 production increased with E.coli urinary tract infection.
  
  
  CONCLUSIONS
  DEFA5 is expressed throughout the urinary tract in non-infected subjects. Specifically, HD5 is expressed throughout the urothelium of the lower urinary tract and in the collecting tubules of the kidney. With infection, HD5 expression increases in the kidney and levels become detectable in the urine. To our knowledge, our findings represent the first to quantitate HD5 expression and production in the human kidney. Moreover, this is the first report to detect the presence of HD5 in infected urine samples. Our results suggest that HD5 may have an important role in maintaining urinary tract sterility.
authors.affiliation: Pediatric Nephrology Fellowship Program, Nationwide Children's Hospital, Columbus, Ohio, United States of America.
authors.forename: John David
authors.initials: JD
authors.lastname: Spencer
authors.forename: David S
authors.initials: DS
authors.lastname: Hains
authors.forename: Edith
authors.initials: E
authors.lastname: Porter
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bevins
authors.forename: Julianne
authors.initials: J
authors.lastname: DiRosario
authors.forename: Brian
authors.initials: B
authors.lastname: Becknell
authors.forename: Huanyu
authors.initials: H
authors.lastname: Wang
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Schwaderer
mesh_terms: D004927:Escherichia coli Infections; D006801:Humans; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000737:chemistry / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011704:Pyelonephritis / Q000378:metabolism; D014551:Urinary Tract / Q000737:chemistry / Q000378:metabolism; D014552:Urinary Tract Infections / Q000378:metabolism*; D019459:Urothelium / Q000737:chemistry / Q000378:metabolism; D023084:alpha-Defensins / Q000032:analysis* / Q000235:genetics / Q000652:urine
chemical_list: C500225:DEFA5 protein, human; D023084:alpha-Defensins