Human beta-defensin-1 Is a Salt-Sensitive Antibiotic in Lung That Is Inactivated in Cystic Fibrosis

Cell. 1997 Feb 21;88(4):553-60. doi: 10.1016/s0092-8674(00)81895-4.

Abstract

A human bronchial xenograft model was used to characterize the molecular basis for the previously described defect in bacterial killing that is present in the cystic fibrosis (CF) lung. Airway surface fluid from CF grafts contained abnormally high NaCl and failed to kill bacteria, defects that were corrected with adenoviral vectors. A full-length clone for the only known human beta-defensin (i.e., hBD-1) was isolated. This gene is expressed throughout the respiratory epithelia of non-CF and CF lungs, and its protein product shows salt-dependent antimicrobial activity to P. aeruginosa. Antisense oligonucleotides to hBD-1 ablated the antimicrobial activity in airway surface fluid from non-CF grafts. These data suggest that hBD-1 plays an important role in innate immunity that is compromised in CF by its salt-dependent inactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / metabolism*
  • Antisense Elements (Genetics) / pharmacology
  • Base Sequence
  • Blood Proteins / drug effects
  • Blood Proteins / genetics
  • Blood Proteins / metabolism*
  • Bronchi / chemistry*
  • Bronchi / pathology
  • Bronchi / transplantation
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis / microbiology
  • Cystic Fibrosis / pathology
  • Defensins
  • Humans
  • Molecular Sequence Data
  • Oligonucleotide Probes / pharmacology
  • RNA, Messenger / analysis
  • Sodium Chloride / metabolism
  • Sodium Chloride / pharmacology*
  • Transplantation, Heterologous
  • beta-Defensins*

Substances

  • Anti-Bacterial Agents
  • Antisense Elements (Genetics)
  • Blood Proteins
  • DEFB1 protein, human
  • Defensins
  • Oligonucleotide Probes
  • RNA, Messenger
  • beta-Defensins
  • Sodium Chloride