The endotoxin-binding bactericidal/permeability-increasing protein (BPI): a target antigen of autoantibodies

J Leukoc Biol. 2001 Apr;69(4):505-12.

Abstract

The bactericidal/permeability-increasing protein (BPI) is an endotoxin-binding neutrophil leukocyte-granule protein with antibacterial and anti-endotoxin properties. A recombinant form of BPI (rBPI21) has been developed and is being tested as a therapeutic agent to treat gram-negative bacterial infections and exposure to gram-negative bacterial endotoxin. BPI is also a target antigen of anti-neutrophil cytoplasmic autoantibodies (ANCA). BPI-ANCA are present in cystic fibrosis, inflammatory bowel disease, vasculitis, and primary sclerosing cholangitis; presence of BPI-ANCA appears associated with a higher inflammatory disease activity and greater organ damage. BPI-ANCA as well as ANCA directed at other neutrophil-granule proteins may exacerbate inflammation by nonspecific effects of extracellular and cell-associated immune complexes. BPI-ANCA may further worsen inflammation by reducing the ability of BPI to promote clearance of gram-negative bacteria and bacterial-associated endotoxin.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Antibodies, Antineutrophil Cytoplasmic / immunology*
  • Antibody Specificity
  • Antimicrobial Cationic Peptides
  • Autoantigens / immunology*
  • Autoimmune Diseases / immunology
  • Blood Proteins / chemistry
  • Blood Proteins / immunology*
  • Child
  • Child, Preschool
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Cytokines / metabolism
  • Cytoplasmic Granules / chemistry
  • Drug Evaluation, Preclinical
  • Endotoxins / metabolism
  • Eosinophils / metabolism
  • Forecasting
  • Gram-Negative Bacterial Infections / drug therapy
  • Humans
  • Infant
  • Inflammation / immunology
  • Membrane Proteins*
  • Mice
  • Multicenter Studies as Topic
  • Neutrophils / metabolism
  • Randomized Controlled Trials as Topic
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / therapeutic use
  • Vasculitis / immunology

Substances

  • Antibodies, Antineutrophil Cytoplasmic
  • Antimicrobial Cationic Peptides
  • Autoantigens
  • Blood Proteins
  • Cytokines
  • Endotoxins
  • Membrane Proteins
  • Recombinant Fusion Proteins
  • bactericidal permeability increasing protein