Identification of a Novel, Multifunctional Beta-Defensin (Human Beta-Defensin 3) With Specific Antimicrobial Activity. Its Interaction With Plasma Membranes of Xenopus Oocytes and the Induction of Macrophage Chemoattraction

Cell Tissue Res. 2001 Nov;306(2):257-64. doi: 10.1007/s004410100433.

Abstract

Previous studies have shown the implication of beta-defensins in host defense of the human body. The human beta-defensins 1 and 2 (hBD-1, hBD-2) have been isolated by biochemical methods. Here we report the identification of a third human beta-defensin, called human beta-defensin 3 (hBD-3; cDNA sequence, Genbank accession no. AF295370), based on bioinformatics and functional genomic analysis. Expression of hBD-3 is detected throughout epithelia of many organs and in non-epithelial tissues. In contrast to hBD-2, which is upregulated by microorganisms or tumor necrosis factor-alpha (TNF-alpha), hBD-3 expression is increased particularly after stimulation by interferon-gamma. Synthetic hBD-3 exhibits a strong antimicrobial activity against gram-negative and gram-positive bacteria and fungi, including Burkholderia cepacia. In addition, hBD-3 activates monocytes and elicits ion channel activity in biomembranes, specifically in oocytes of Xenopus laevis. This paper also shows that screening of genomic sequences is a valuable tool with which to identify novel regulatory peptides. Human beta-defensins represent a family of antimicrobial peptides differentially expressed in most tissues, regulated by specific mechanisms, and exerting physiological functions not only related to direct host defense.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Burkholderia cepacia / drug effects
  • Cell Line
  • Cell Membrane / metabolism*
  • Chemotaxis / physiology*
  • Epithelial Cells / physiology
  • Gene Expression Regulation
  • Humans
  • Ion Channels / metabolism
  • Macrophages / physiology*
  • Molecular Sequence Data
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Oocytes
  • Patch-Clamp Techniques
  • Sequence Alignment
  • Xenopus laevis
  • beta-Defensins / chemistry
  • beta-Defensins / genetics
  • beta-Defensins / metabolism*
  • beta-Defensins / pharmacology*

Substances

  • Anti-Bacterial Agents
  • DEFB103A protein, human
  • Ion Channels
  • beta-Defensins

Associated data

  • GENBANK/AF295370