Differential expression of alpha- and beta-defensins in human peripheral blood

Eur J Clin Invest. 2003 Jan;33(1):82-7. doi: 10.1046/j.1365-2362.2003.01076.x.

Abstract

Background: Human defensin peptides with broad-spectrum antimicrobial activity have been implicated in the human defence response towards microbial invasion. Two families of defensins designated alpha- and beta-defensins, respectively, have been identified. Little is known about the expression of both defensin families in human peripheral blood. The purpose of this study was to examine the expression of alpha- and beta-defensin genes in human peripheral blood.

Material and methods: Fifty-one healthy blood donors were screened for defensin expression. Blood from defensin responders was stimulated by lipopolysaccharide or heat-inactivated Pseudomonas aeruginosa ex vivo. Levels of mRNA were assessed by semiquantitative RT-PCR. Southern blot analysis and sequencing were used to confirm the identity of defensin gene transcripts. Western blotting analysis was used to detect the expression of defensin peptides.

Results: beta-defensin was undetected in human peripheral blood without stimulation. Following stimulation by lipopolysaccharide or heat-inactivated bacterial cells, the majority (88.2%) of healthy individuals had a detectable expression for beta-defensin-1 gene and 39.2% for beta-defensin-2 gene, compared with none for beta-defensin-3. beta-defensin-1 and -2 mRNAs in the stimulated human peripheral blood of responders became detectable at 3 h and showed a maximum at 6 h following induction by 100 ng mL-1 of lipopolysaccharide or bacterial cells. In contrast, human alpha-defensins 1-3 mRNA are constitutively expressed in peripheral leukocytes but not up-regulated by lipopolysaccharide or bacterial cells.

Conclusions: In human peripheral blood, beta-defensin-1 and -2 genes were transiently transcribed and translated following the induction of lipopolysaccharide or heat-inactivated bacterial cells, whereas alpha-defensins 1-3 genes were constitutively transcribed, and beta-defensin-3 gene was not expressed. The inducible expression of beta-defensin-1 and -2 genes showed interindividual variability.

MeSH terms

  • Adult
  • Antigens, Bacterial / immunology
  • Gene Expression Regulation / immunology*
  • Humans
  • In Vitro Techniques
  • Leukocytes / metabolism
  • Lipopolysaccharides / immunology
  • Pseudomonas aeruginosa / immunology
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • alpha-Defensins / blood
  • alpha-Defensins / genetics*
  • beta-Defensins / blood
  • beta-Defensins / genetics*

Substances

  • Antigens, Bacterial
  • Lipopolysaccharides
  • RNA, Messenger
  • alpha-Defensins
  • beta-Defensins