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