Affinage

BPI

Bactericidal permeability-increasing protein · UniProt P17213

Length
487 aa
Mass
53.9 kDa
Annotated
2026-04-28
100 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BPI is an innate immune effector protein stored in azurophil granules of neutrophils and expressed on mucosal epithelial surfaces that kills Gram-negative bacteria and neutralizes lipopolysaccharide (LPS). Its boomerang-shaped structure contains two domains with apolar lipid-binding pockets; the highly basic N-terminal domain binds LPS with nanomolar affinity through electrostatic interactions with LPS phosphate groups, inserts into the bacterial outer membrane to cause rigidification, membrane rupture, and inner membrane damage leading to bacterial killing, while simultaneously forming stable BPI–LPS complexes that block all downstream LPS-induced host cell signaling (PMID:9188532, PMID:9254629, PMID:9254630, PMID:8330906). The C-terminal domain is required for intracellular granule storage, protein stability during sorting, and opsonization functions (PMID:11073106). BPI transcription during granulocyte maturation is driven by C/EBPβ and C/EBPε binding to its proximal promoter, and in intestinal epithelial cells BPI expression is induced by membrane damage-triggered potassium efflux through a p38-dependent pathway (PMID:16684888, PMID:28861073). Beyond antimicrobial defense, BPI selectively induces apoptosis in vascular endothelial cells to inhibit angiogenesis and negatively regulates regulatory T cell differentiation when present in T-cell-derived exosomes (PMID:10891448, PMID:34815797).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1993 High

    Establishing that the N-terminal ~25 kDa fragment is sufficient for both bactericidal and LPS-neutralizing activity, with nanomolar LPS-binding affinity, defined the minimal functional unit and showed that a single protein domain could account for BPI's dual antimicrobial and anti-endotoxin functions.

    Evidence In vitro bactericidal assays, LPS-binding assays with proteolytic/recombinant N-terminal fragments, and ex vivo whole blood cytokine assays

    PMID:8330906

    Open questions at the time
    • Structural basis for N-terminal LPS recognition not yet resolved
    • Mechanism of bacterial killing beyond initial binding unknown
    • Role of C-terminal domain undefined
  2. 1995 Medium

    Demonstrating that BPI's anti-endotoxin potency depends on LPS polysaccharide chain length (complete inhibition of smooth LPS vs. partial for rough LPS) revealed that the LPS–BPI interaction is not solely lipid A-mediated and involves polysaccharide determinants.

    Evidence In vitro monocyte TNF induction assay with graded LPS variants and rBPI

    PMID:7543211

    Open questions at the time
    • Molecular contacts between BPI and LPS polysaccharide chains unresolved
    • In vivo relevance of chain-length dependence not tested
  3. 1997 High

    The crystal structure of BPI revealed a boomerang-shaped two-domain fold with apolar lipid-binding pockets on the concave surface, providing the first atomic framework for understanding LPS binding and membrane insertion, while biophysical studies showed that BPI inserts into negatively charged membranes via electrostatic displacement of divalent cations, rigidifies LPS acyl chains, and causes membrane rupture.

    Evidence X-ray crystallography at 2.4 Å (subsequently 1.7 Å); monolayer insertion experiments; IR spectroscopy; laser Doppler velocimetry; planar bilayer electrophysiology

    PMID:10843855 PMID:9188532 PMID:9254629 PMID:9254630

    Open questions at the time
    • No co-crystal of BPI bound to LPS
    • Inner membrane damage mechanism not structurally explained
    • Lipid-binding pocket occupancy in vivo unknown
  4. 1997 High

    Showing that BPI enhances LPS aggregation (opposite to LBP's dispersal) and inhibits LBP–LPS binding at substoichiometric ratios clarified how BPI competes with LBP to intercept LPS signaling rather than simply scavenging free LPS.

    Evidence Sedimentation, light scattering, and fluorescence analyses of LPS–protein complexes

    PMID:9228038

    Open questions at the time
    • Structure of the BPI–LPS aggregate complex unresolved
    • Stoichiometry and kinetics in physiological fluids not determined
  5. 1998 High

    Structure-based identification of a conserved cluster of basic residues (Lys42, 48, 92, 95, 99) at the N-terminal tip, together with subcellular localization of BPI to azurophil granules with functional validation via blocking antibodies, established that BPI is the principal neutrophil bactericidal factor operating through electrostatic contacts with LPS phosphate groups.

    Evidence Conserved residue mapping onto crystal structure; granule fractionation; BPI-blocking antibody functional assays; bacterial membrane damage assays

    PMID:9568897 PMID:9665269

    Open questions at the time
    • Mutational validation of individual lysine contributions to bactericidal activity not performed
    • Relative contributions of BPI vs. other granule proteins in vivo unquantified
  6. 2000 Medium

    Demonstrating that the C-terminal domain is required for granule storage and protects against proteasomal degradation during intracellular sorting defined a non-redundant function for the C-terminal domain distinct from the N-terminal bactericidal role.

    Evidence cDNA transfection of deletion mutants and chimeras into myeloid cell lines; subcellular fractionation and protein stability assays

    PMID:11073106

    Open questions at the time
    • Sorting receptor or signal recognized by C-terminal domain not identified
    • Opsonization mechanism of C-terminal domain not structurally defined
  7. 2000 Medium

    Immunoelectron microscopy showed BPI is membrane-associated within azurophil granules and relocates to phagosomes upon activation, with eosinophils also delivering BPI to phagosomes, establishing granule-to-phagosome delivery as the physiological mechanism for intracellular bacterial killing.

    Evidence Cryotechnique immunoelectron microscopy; selective granule-release experiments; phagocytosis assays in neutrophils and eosinophils

    PMID:10752689 PMID:9616176

    Open questions at the time
    • Mode of BPI membrane association within granules unknown
    • Relative bactericidal contribution of phagosomal BPI vs. other granule contents not quantified
  8. 2000 Medium

    The finding that BPI selectively induces apoptosis in endothelial cells and inhibits angiogenesis in vitro and in vivo expanded BPI's functional repertoire beyond antimicrobial defense to vascular biology.

    Evidence Flow cytometry for apoptosis; collagen gel tube formation assay; in vivo chick chorioallantoic membrane angiogenesis assay

    PMID:10891448

    Open questions at the time
    • Receptor or mechanism of EC-selective apoptosis induction unknown
    • Physiological context for anti-angiogenic function not established
  9. 2002 High

    Identification of BPI expression on mucosal epithelial cell surfaces, induced by aspirin-triggered lipoxins and functional in blocking LPS signaling and killing bacteria, established BPI as an epithelial antimicrobial effector independent of neutrophils.

    Evidence Microarray and RT-PCR; immunostaining for surface localization; functional neutralization with BPI antiserum; tissue immunohistochemistry

    PMID:11891303

    Open questions at the time
    • Mechanism of BPI surface tethering on epithelia not defined
    • Epithelial BPI contribution relative to other antimicrobial peptides unknown
  10. 2006 High

    ChIP and EMSA demonstrated direct binding of C/EBPβ and C/EBPε to the BPI promoter during retinoic acid-induced granulocyte differentiation, establishing the transcriptional regulation mechanism for myeloid BPI expression.

    Evidence ATRA treatment of NB4 cells; cycloheximide block; EMSA; chromatin immunoprecipitation

    PMID:16684888

    Open questions at the time
    • Cis-regulatory elements sufficient for granulocyte-specific expression not fully mapped
    • Whether same factors regulate epithelial BPI expression unknown
  11. 2016 Medium

    A 27-amino acid N-terminal BPI peptide disrupted enveloped virus particles with human-sequence specificity (lost in mouse homolog), extending BPI's antimicrobial reach to antiviral defense against Influenza A and VSV.

    Evidence Antiviral infectivity assays across multiple influenza strains; electron microscopy of virus particles; human-to-mouse sequence substitution

    PMID:27273104

    Open questions at the time
    • In vivo antiviral role not demonstrated
    • Molecular basis of species-specific antiviral activity unresolved
  12. 2017 Medium

    Intracellular potassium efflux caused by pore-forming toxins or bacterial infection was identified as the danger signal inducing epithelial BPI expression through a p38-dependent pathway, defining a damage-sensing circuit upstream of BPI.

    Evidence Caco-2 cells treated with pore-forming toxins; in vivo mouse infection with Salmonella and Shigella; p38 inhibitor studies

    PMID:28861073

    Open questions at the time
    • Transcription factor downstream of p38 that activates BPI in epithelia not identified
    • Whether potassium sensing feeds through inflammasome components not tested
  13. 2021 Medium

    BPI overexpression in T cells suppressed Treg differentiation and BPI-containing exosomes stimulated macrophage IL-1β and systemic inflammation, revealing an unexpected immunoregulatory function for BPI in adaptive immunity.

    Evidence T-cell-specific BPI transgenic and KO mice; adoptive exosome transfer; scRNA-seq; in vitro Treg differentiation assays

    PMID:34815797

    Open questions at the time
    • Molecular mechanism by which BPI inhibits Treg differentiation not defined beyond ZFP36L2/Helios correlation
    • Physiological relevance of T-cell BPI expression in humans unknown
    • Single lab observation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic structure of the BPI–LPS complex, the receptor or mechanism for BPI's selective endothelial cell apoptosis, the identity of the epithelial BPI surface anchor, and whether BPI's immunoregulatory functions in T cells operate through the same lipid-binding mechanism as its antimicrobial activity.
  • No BPI–LPS co-crystal structure
  • Endothelial receptor for BPI-induced apoptosis unknown
  • Mechanism of BPI surface retention on epithelia undefined
  • Link between lipid-binding pockets and Treg regulation not tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 5 GO:0090729 toxin activity 4
Localization
GO:0031410 cytoplasmic vesicle 4 GO:0005576 extracellular region 3 GO:0005886 plasma membrane 2
Pathway
R-HSA-168256 Immune System 5 R-HSA-5357801 Programmed Cell Death 1
Partners
CEBPBCEBPELBP

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Crystal structure of human BPI at 2.4 Å resolution reveals a boomerang-shaped molecule with two similar domains, each containing an apolar lipid-binding pocket on the concave surface that binds phosphatidylcholine acyl chains, suggesting these pockets bind LPS acyl chains to mediate LPS neutralization. X-ray crystallography with bound phospholipid ligands Science High 9188532
2000 Extended crystal structure of human BPI resolved to 1.7 Å; structural comparison of the two domains (same fold, <13% sequence identity) using 3D-1D profiles identified residue pairs with conserved structural roles despite dissimilar sequences, clarifying the mechanism of fold conservation. X-ray crystallography at 1.7 Å; 3D-1D profile structural analysis Journal of Molecular Biology High 10843855
1998 Structure/function analysis of conserved residues in BPI and LBP, using the BPI crystal structure, identified a cluster of conserved positively charged residues (Lys42, 48, 92, 95, 99) at the tip of the N-terminal domain with no structural role, predicted to make electrostatic contacts with negatively charged LPS groups and responsible for BPI's bactericidal activity. Structural analysis of conserved residues mapped onto crystal structure; comparison with known LPS-binding mutagenesis data Protein Science High 9568897
1993 The antibacterial and LPS-neutralizing activities of BPI are fully expressed by the N-terminal ~25 kDa fragment; BPI binds LPS with high affinity (apparent Kd 2–5 nM) and this complex formation with cell-associated or cell-free LPS inhibits all LPS-induced host cell responses. In vitro bactericidal assays; LPS-binding assays with proteolytic/recombinant N-terminal BPI fragments; whole blood ex vivo cytokine assays Immunobiology High 8330906
1998 BPI is stored in azurophil (primary) granules of neutrophils; BPI-blocking antibodies abolish antibacterial activity of whole PMN lysates; binding of BPI to live bacteria via LPS causes immediate growth arrest, with killing coinciding with later inner membrane damage. Granule fractionation; BPI-blocking antibody functional assays; bacterial killing and membrane damage assays Journal of Leukocyte Biology High 9665269
1997 LBP disperses LPS aggregates whereas BPI enhances sedimentation velocity and apparent size of LPS aggregates; BPI inhibits LPS–LBP binding even at very low (1:40–1:20) BPI:LPS molar ratios; the two proteins form physically distinct types of complexes with LPS. Sedimentation, light scattering, and fluorescence analyses of LPS–protein complexes Journal of Biological Chemistry High 9228038
1997 The recombinant N-terminal BPI fragment (rBPI21) incorporates into negatively charged LPS and phosphatidylglycerol monolayers/bilayers but not neutral phosphatidylcholine; it rigidifies acyl chains and immobilizes phosphate groups of LPS aggregates, reducing zeta-potential; high Mg2+ ions protect against this action, suggesting electrostatic displacement as the initial step. Monolayer experiments, infrared spectroscopy, resonance energy transfer spectroscopy, laser Doppler velocimetry Biochemistry High 9254629
1997 rBPI21 causes membrane rupture and increases membrane current when added to the LPS leaflet of asymmetric LPS/phospholipid bilayer membranes; it shifts the transmembrane potential of outer membrane models; 40 mM MgCl2 significantly reduces this effect, supporting an electrostatic mechanism of outer membrane disruption. Electrical measurements on planar bilayer membranes reconstituted with deep-rough LPS Biochemistry High 9254630
1998 BPI is present in specific granules of human eosinophils (detected by immunoelectron microscopy) and is released into phagosomes upon phagocytosis, indicating granule-to-phagosome delivery as a mechanism for antibacterial action in eosinophils. Immunoelectron microscopy; Western blot; ELISA quantification Blood Medium 9616176
2000 BPI is membrane-associated within azurophil granules of neutrophils (co-localizing with MPO and CD63); upon cellular activation by ionophore or phagocytosis, BPI is relocated to phagosomes via granule–endosome fusion, following the same route as MPO and CD63. Cryotechnique immunoelectron microscopy; selective granule-release experiments with monensin; phagocytosis assays APMIS Medium 10752689
2000 The C-terminal domain of BPI is required for granule storage and protects against degradation during intracellular sorting; deletion of the N-terminal half causes retention in the ER and proteasomal degradation; chimeras confirm that C-terminal BPI domain confers stability for storage in myeloid cells. cDNA transfection into rodent hematopoietic cell lines; deletion mutants and chimeras; subcellular fractionation and protein stability assays Journal of Leukocyte Biology Medium 11073106
2002 BPI is expressed on the cell surface of human mucosal epithelial cells and is transcriptionally induced by aspirin-triggered lipoxins (ATLa); surface-expressed epithelial BPI blocks LPS-mediated signaling and kills Salmonella typhimurium, functioning as an antimicrobial/endotoxin shield. Microarray + RT-PCR; cell surface localization by immunostaining; functional assays with BPI-neutralizing antiserum; in vivo tissue IHC PNAS High 11891303
2000 BPI inhibits angiogenesis by inducing apoptosis selectively in vascular endothelial cells; apoptosis is mediated by cell detachment and is EC-specific (not fibroblast or other cell types); BPI inhibits tube formation in collagen gel assays and vessel formation in the CAM assay at nanomolar concentrations. Flow cytometry (subdiploid cell quantification); nuclear fragmentation assay; in vitro collagen gel angiogenesis assay; in vivo CAM assay Blood Medium 10891448
2006 All-trans retinoic acid (ATRA) induces BPI expression in NB4 promyelocytic cells through de novo protein synthesis; induction correlates with direct binding of C/EBPβ and C/EBPε transcription factors to the proximal BPI promoter, as demonstrated by EMSA and chromatin immunoprecipitation. ATRA treatment of NB4 cells; cycloheximide sensitivity; EMSA; chromatin immunoprecipitation (ChIP) Journal of Leukocyte Biology High 16684888
2021 BPI overexpression in T cells suppresses Treg differentiation; BPI-containing T-cell-derived exosomes stimulate IL-1β expression in recipient macrophages; adoptive transfer of BPI-containing exosomes induces systemic inflammation, autoantibody production, and multi-organ damage in mice; BPI knockout enhances Treg differentiation in vitro, identifying BPI as a negative regulator of Treg differentiation associated with ZFP36L2 upregulation and Helios downregulation. T-cell-specific BPI transgenic mice; adoptive exosome transfer; scRNA-seq; in vitro Treg differentiation with BPI KO and overexpression Theranostics Medium 34815797
2017 BPI expression in intestinal epithelial cells is induced by cell membrane damage (via pore-forming toxins and bacterial infection); the signal for induction is a drop in intracellular potassium acting as a danger-associated molecular pattern, activating BPI expression in a p38-dependent manner. Caco-2 cell treatment with pore-forming toxins and bacteria; in vivo infection of mice with Salmonella Typhimurium, Shigella, and non-invasive mutants; p38 inhibitor studies Frontiers in Microbiology Medium 28861073
2016 A 27-amino acid peptide from the N-terminal portion of human BPI inhibits infectivity of multiple Influenza A strains (H1N1, H3N2, H5N1) and Vesicular Stomatitis Virus by disrupting the virus envelope; changing human BPI peptide sequence to the mouse homolog abolishes antiviral activity, demonstrating human-BPI-sequence-specific antiviral mechanism. Antiviral infectivity assays; electron microscopy of virus particles; human-to-mouse sequence substitution experiments PloS One Medium 27273104
1995 rBPI inhibits LPS-induced TNF production from monocytes in a polysaccharide chain length–dependent manner: smooth LPS (S-form)-induced TNF is completely inhibited, Re 595 LPS only partially, and lipid A DP not at all, demonstrating that BPI's anti-endotoxin mechanism depends on the LPS polysaccharide structure. In vitro monocyte TNF induction assay with rBPI, rLBP, rCD14 and anti-CD14 antibodies; graded LPS polysaccharide chain lengths Scandinavian Journal of Immunology Medium 7543211
2004 Murine BPI (53% identity to human BPI) is expressed in testis, epididymis and bone marrow (not predominantly in neutrophils as in humans); murine BPI expressed in HEK293 cells retains antibacterial activity against E. coli comparable to human BPI; retinoic acid enhances BPI expression in promyelocytic cells. cDNA cloning; RT-PCR tissue expression; overexpression in HEK293 cells with bacterial killing assay; ATRA treatment Journal of Leukocyte Biology Medium 15590754
2019 Immune complexes of BPI and BPI-ANCA (but not BPI-ANCA alone) induce TNFα-dependent NET formation with histone hypercitrullination in neutrophils; TNFα upregulates BPI expression in neutrophils and causes BPI translocation to the cell surface, creating the substrate for immune complex formation. In vitro NET formation assay; immunofluorescent imaging of citrullinated histones; flow cytometry of BPI surface expression Frontiers in Immunology Medium 31249574

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Crystal structure of human BPI and two bound phospholipids at 2.4 angstrom resolution. Science (New York, N.Y.) 306 9188532
2002 Lipid mediator-induced expression of bactericidal/ permeability-increasing protein (BPI) in human mucosal epithelia. Proceedings of the National Academy of Sciences of the United States of America 228 11891303
2003 Bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP): structure, function and regulation in host defence against Gram-negative bacteria. Biochemical Society transactions 162 12887306
1995 Bactericidal/permeability-increasing protein (BPI) is an important antigen for anti-neutrophil cytoplasmic autoantibodies (ANCA) in vasculitis. Clinical and experimental immunology 152 7813109
1998 The bactericidal/permeability-increasing protein (BPI) in antibacterial host defense. Journal of leukocyte biology 126 9665269
1993 The bactericidal/permeability-increasing protein (BPI), a potent element in host-defense against gram-negative bacteria and lipopolysaccharide. Immunobiology 124 8330906
2011 Icotinib (BPI-2009H), a novel EGFR tyrosine kinase inhibitor, displays potent efficacy in preclinical studies. Lung cancer (Amsterdam, Netherlands) 120 22112293
1998 The BPI/LBP family of proteins: a structural analysis of conserved regions. Protein science : a publication of the Protein Society 118 9568897
2004 Meet the relatives: a family of BPI- and LBP-related proteins. Trends in immunology 108 15106612
1996 Anti-neutrophil cytoplasmic antibodies (ANCA) directed against bactericidal/permeability increasing protein (BPI): a new seromarker for inflammatory bowel disease and associated disorders. Clinical and experimental immunology 108 8603534
2007 Evidence of a bactericidal permeability increasing protein in an invertebrate, the Crassostrea gigas Cg-BPI. Proceedings of the National Academy of Sciences of the United States of America 105 17965238
1997 Lipopolysaccharide (LPS)-binding proteins BPI and LBP form different types of complexes with LPS. The Journal of biological chemistry 95 9228038
2007 The bactericidal/permeability-increasing protein (BPI) in infection and inflammatory disease. Clinica chimica acta; international journal of clinical chemistry 91 17678885
2010 Phase I study of icotinib hydrochloride (BPI-2009H), an oral EGFR tyrosine kinase inhibitor, in patients with advanced NSCLC and other solid tumors. Lung cancer (Amsterdam, Netherlands) 87 21144613
2008 Bactericidal/permeability-increasing protein (BPI) and BPI homologs at mucosal sites. Trends in immunology 66 18838299
2000 Bactericidal/permeability-increasing protein (BPI) inhibits angiogenesis via induction of apoptosis in vascular endothelial cells. Blood 65 10891448
2005 Characterization and expression analysis of bactericidal permeability-increasing protein (BPI) antimicrobial peptide gene from channel catfish Ictalurus punctatus. Developmental and comparative immunology 62 15896843
2011 LBP/BPI proteins and their relatives: conservation over evolution and roles in mutualism. Biochemical Society transactions 61 21787344
2011 Systematic nomenclature for the PLUNC/PSP/BSP30/SMGB proteins as a subfamily of the BPI fold-containing superfamily. Biochemical Society transactions 56 21787333
2011 Distribution of human PLUNC/BPI fold-containing (BPIF) proteins. Biochemical Society transactions 54 21787341
1999 Anti-neutrophil cytoplasmic antibodies (ANCA) against bactericidal/permeability-increasing protein (BPI) and cystic fibrosis lung disease. Clinical and experimental immunology 54 10469063
1997 The genomic organization of the genes for human lipopolysaccharide binding protein (LBP) and bactericidal permeability increasing protein (BPI) is highly conserved. Biochemical and biophysical research communications 54 9240454
1998 The bactericidal/permeability-increasing protein (BPI) is present in specific granules of human eosinophils. Blood 53 9616176
1997 Mechanisms of action of the bactericidal/permeability-increasing protein BPI on endotoxin and phospholipid monolayers and aggregates. Biochemistry 50 9254629
2004 Cloning and analyses of a BPI/LBP cDNA of the Atlantic cod (Gadus morhua L.). Developmental and comparative immunology 47 14698217
2006 From infection to autoimmunity: a new model for induction of ANCA against the bactericidal/permeability increasing protein (BPI). Autoimmunity reviews 45 17317612
1997 Mechanisms of action of bactericidal/permeability-increasing protein BPI on reconstituted outer membranes of gram-negative bacteria. Biochemistry 45 9254630
2013 Parental transfer of the antimicrobial protein LBP/BPI protects Biomphalaria glabrata eggs against oomycete infections. PLoS pathogens 44 24367257
2000 The 1.7 A crystal structure of BPI: a study of how two dissimilar amino acid sequences can adopt the same fold. Journal of molecular biology 43 10843855
1993 The genes for the lipopolysaccharide binding protein (LBP) and the bactericidal permeability increasing protein (BPI) are encoded in the same region of human chromosome 20. Genomics 43 8432532
2003 Expression of BPI (bactericidal/permeability-increasing protein) in human mucosal epithelia. Biochemical Society transactions 42 12887308
1995 Prospects for use of recombinant BPI in the treatment of gram-negative bacterial infections. Infectious agents and disease 41 7613727
2003 Structure of human BPI (bactericidal/permeability-increasing protein) and implications for related proteins. Biochemical Society transactions 40 12887307
2003 Four BPI (bactericidal/permeability-increasing protein)-like genes expressed in the mouse nasal, oral, airway and digestive epithelia. Biochemical Society transactions 40 12887309
2021 BPI overexpression suppresses Treg differentiation and induces exosome-mediated inflammation in systemic lupus erythematosus. Theranostics 38 34815797
2006 Autoantibody response to BPI predict disease severity and outcome in cystic fibrosis. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 38 17166780
2011 The second bactericidal permeability increasing protein (BPI) and its revelation of the gene duplication in the Pacific oyster, Crassostrea gigas. Fish & shellfish immunology 37 21300156
2018 BPI-9016M, a c-Met inhibitor, suppresses tumor cell growth, migration and invasion of lung adenocarcinoma via miR203-DKK1. Theranostics 33 30613269
2011 Distant cousins: genomic and sequence diversity within the BPI fold-containing (BPIF)/PLUNC protein family. Biochemical Society transactions 33 21787330
2003 Molecular cloning of a novel bactericidal permeability-increasing protein/lipopolysaccharide-binding protein (BPI/LBP) from common carp Cyprinus carpio L. and its expression. Molecular immunology 33 12943799
2004 A murine antibacterial ortholog to human bactericidal/permeability-increasing protein (BPI) is expressed in testis, epididymis, and bone marrow. Journal of leukocyte biology 32 15590754
2011 Pseudomonas aeruginosa in cystic fibrosis: pyocyanin negative strains are associated with BPI-ANCA and progressive lung disease. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 31 21463973
1993 Plasma levels of bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding protein (LBP) during hemodialysis. Clinical nephrology 31 7507806
2015 Cloning and characterization of two lipopolysaccharide-binding protein/bactericidal permeability-increasing protein (LBP/BPI) genes from the sea cucumber Apostichopus japonicus with diversified function in modulating ROS production. Developmental and comparative immunology 30 25956196
2011 Antigen-specific blocking of CD4-specific immunological synapse formation using BPI and current therapies for autoimmune diseases. Medicinal research reviews 30 21433035
2001 The endotoxin-binding bactericidal/permeability-increasing protein (BPI): a target antigen of autoantibodies. Journal of leukocyte biology 30 11310835
1994 Anti-endotoxin therapy in primate bacteremia with HA-1A and BPI. Annals of surgery 30 8024362
2011 Ovocalyxin-36 and other LBP/BPI/PLUNC-like proteins as molecular actors of the mechanisms of the avian egg natural defences. Biochemical Society transactions 28 21787332
2010 Identification and characterisation of the BPI/LBP/PLUNC-like gene repertoire in chickens reveals the absence of a LBP gene. Developmental and comparative immunology 28 20959152
2003 Expansion of the BPI family by duplication on human chromosome 20: characterization of the RY gene cluster in 20q11.21 encoding olfactory transporters/antimicrobial-like peptides. Genomics 27 12837268
2003 Pseudomonas-induced lung damage in cystic fibrosis correlates to bactericidal-permeability increasing protein (BPI)-autoantibodies. Clinical and experimental rheumatology 27 14740434
2000 Bactericidal/permeability-increasing protein (BPI) in sepsis correlates with the severity of sepsis and the outcome. Intensive care medicine 27 11089749
2022 Efficacy and Safety of Rezivertinib (BPI-7711) in Patients With Locally Advanced or Metastatic/Recurrent EGFR T790M-Mutated NSCLC: A Phase 2b Study. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 26 36049654
2000 Anti-neutrophil cytoplasmic antibodies directed against the bactericidal/permeability-increasing protein (BPI) in pediatric cystic fibrosis patients do not recognize N-terminal regions important for the anti-microbial and lipopolysaccharide-binding activity of BPI. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 26 10893006
1996 Frequency of anti-bactericidal/permeability-increasing protein (BPI) and anti-azurocidin in patients with renal disease. Clinical and experimental immunology 26 8697620
2021 Killing three birds with one BPI: Bactericidal, opsonic, and anti-inflammatory functions. Journal of translational autoimmunity 25 34142075
2014 Antimicrobial activity of peptides derived from olive flounder lipopolysaccharide binding protein/bactericidal permeability-increasing protein (LBP/BPI). Marine drugs 25 25329706
1995 Influence of CD14, LBP and BPI in the monocyte response to LPS of different polysaccharide chain length. Scandinavian journal of immunology 24 7543211
2016 Arabidopsis LBP/BPI related-1 and -2 bind to LPS directly and regulate PR1 expression. Scientific reports 23 27273538
2003 BPI-ANCA in transporter associated with antigen presentation (TAP) deficiency: possible role in susceptibility to Gram-negative bacterial infections. Clinical and experimental immunology 23 12869032
2000 The bactericidal/permeability-increasing protein (BPI) is membrane-associated in azurophil granules of human neutrophils, and relocation occurs upon cellular activation. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 23 10752689
2017 BPI Fold-Containing Family A Member 2/Parotid Secretory Protein Is an Early Biomarker of AKI. Journal of the American Society of Nephrology : JASN 22 28775000
2015 The LBP/BPI multigenic family in invertebrates: Evolutionary history and evidences of specialization in mollusks. Developmental and comparative immunology 22 26608112
2013 Identification and expression analysis on bactericidal permeability-increasing protein (BPI)/lipopolysaccharide-binding protein (LBP) of ark shell, Scapharca broughtonii. Fish & shellfish immunology 22 23742867
2004 BPI-ANCA of pediatric cystic fibrosis patients can impair BPI-mediated killing of E. coli DH5alpha in vitro. Pediatric pulmonology 22 14730661
2022 Safety, Efficacy, and Pharmacokinetics of Rezivertinib (BPI-7711) in Patients With Advanced NSCLC With EGFR T790M Mutation: A Phase 1 Dose-Escalation and Dose-Expansion Study. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 21 35181498
2015 LBP/BPI homologue in Eisenia andrei earthworms. Developmental and comparative immunology 21 26297397
2006 mRNA expression patterns of the BPI/LBP molecule in the Atlantic cod (Gadus morhua L.). Fish & shellfish immunology 21 17442589
2020 First-in-human phase I study of BPI-9016M, a dual MET/Axl inhibitor, in patients with non-small cell lung cancer. Journal of hematology & oncology 20 31948451
2013 Ubiquitin ligase Cbl-b is involved in icotinib (BPI-2009H)-induced apoptosis and G1 phase arrest of EGFR mutation-positive non-small-cell lung cancer. BioMed research international 19 23586056
2004 Identification of a novel left-right asymmetrically expressed gene in the mouse belonging to the BPI/PLUNC superfamily. Developmental dynamics : an official publication of the American Association of Anatomists 19 14745963
2013 Genetic variation in exon 10 of the BPI gene is associated with Escherichia coli F18 susceptibility in Sutai piglets. Gene 18 23562783
2012 Molecular identification and expression analysis of two distinct BPI/LBPs (bactericidal permeability-increasing protein/LPS-binding protein) from rock bream, Oplegnathus fasciatus. Fish & shellfish immunology 18 22521422
2007 Expansion of the Bactericidal/Permeability Increasing-like (BPI-like) protein locus in cattle. BMC genomics 18 17362520
2007 The bovine salivary proteins BSP30a and BSP30b are independently expressed BPI-like proteins with anti-Pseudomonas activity. Molecular immunology 18 18055015
2005 A polymorphism of the bactericidal/permeability increasing protein (BPI) gene is associated with Crohn's disease. Journal of clinical gastroenterology 18 15758620
2010 Genetic variations of interleukin-23R (1143A>G) and BPI (A645G), but not of NOD2, are associated with acute graft-versus-host disease after allogeneic transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 17 20541026
2010 Association between bactericidal/permeability increasing protein (BPI) gene polymorphism (Lys216Glu) and inflammatory bowel disease. Journal of Crohn's & colitis 17 21272798
2009 Molecular cloning and characterization of LPS-binding protein/bactericidal permeability-increasing protein (LBP/BPI) from olive flounder, Paralichthys olivaceus. Veterinary immunology and immunopathology 17 19698997
2008 Characterization of the BPI-like gene from a subtracted cDNA library of large yellow croaker (Pseudosciaena crocea) and induced expression by formalin-inactivated Vibrio alginolyticus and Nocardia seriolae vaccine challenges. Fish & shellfish immunology 17 18952461
2005 Autoantibodies against bactericidal/permeability-increasing protein (BPI-ANCA) in cystic fibrosis patients treated with azithromycin. Clinical and experimental medicine 16 16096858
2001 Analysis of intractable factors in chronic airway infections: role of the autoimmunity induced by BPI-ANCA. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 15 11810589
2000 BPI-ANCA is found in reactive arthritis caused by Yersinia and Salmonella infection and recognise exclusively the C-terminal part of the BPI molecule. Scandinavian journal of rheumatology 15 11028843
1997 Use of native and recombinant bactericidal/permeability-increasing proteins (BPI) as antigens for detection of BPI-ANCA. Journal of immunological methods 15 9294593
2017 Epithelial Cell Damage Activates Bactericidal/Permeability Increasing-Protein (BPI) Expression in Intestinal Epithelium. Frontiers in microbiology 14 28861073
2016 The Human Antimicrobial Protein Bactericidal/Permeability-Increasing Protein (BPI) Inhibits the Infectivity of Influenza A Virus. PloS one 14 27273104
2012 Extensive endoscopic image-guided sinus surgery decreases BPI-ANCA in patients with cystic fibrosis. Scandinavian journal of immunology 14 22946777
2011 The BPI-like/PLUNC family proteins in cattle. Biochemical Society transactions 14 21787338
2023 Results of the phase IIa study to evaluate the efficacy and safety of rezivertinib (BPI-7711) for the first-line treatment of locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation from a phase I/IIa study. BMC medicine 13 36617560
2015 BPI-ANCA Provides Additional Clinical Information to Anti-Pseudomonas Serology: Results from a Cohort of 117 Swedish Cystic Fibrosis Patients. Journal of immunology research 13 26273683
2006 All-trans retinoic acid-induced expression of bactericidal/permeability-increasing protein (BPI) in human myeloid cells correlates to binding of C/EBPbeta and C/EBPepsilon to the BPI promoter. Journal of leukocyte biology 13 16684888
2003 ANCA against the bactericidal/permeability increasing protein (BPI-ANCA) can compromise the antibiotic function of BPI in a Wegener's granulomatosis patient. Clinical and experimental rheumatology 13 14740457
2024 BPI-GNN: Interpretable brain network-based psychiatric diagnosis and subtyping. NeuroImage 12 38569980
2021 Molecular characterization and functional analysis of the bactericidal permeability-increasing protein/LPS-binding protein (BPI/LBP) from roughskin sculpin (Trachidermus fasciatus). Developmental and comparative immunology 12 34000320
2019 The Pathogenicity of BPI-ANCA in a Patient With Systemic Vasculitis. Frontiers in immunology 11 31249574
2011 The bactericidal/permeability-increasing protein (BPI) in the innate defence of the lower airways. Biochemical Society transactions 11 21787345
2007 A peptide derived from human bactericidal/permeability-increasing protein (BPI) exerts bactericidal activity against Gram-negative bacterial isolates obtained from clinical cases of bovine mastitis. Veterinary microbiology 11 17560054
2005 Association study of Wegener granulomatosis and the functionally relevant A645G polymorphism in the bactericidal/permeability increasing protein (BPI) gene. International journal of immunogenetics 11 15686586
2002 The antiangiogenic properties of bactericidal/permeability-increasing protein (BPI). Annals of medicine 11 12014429
2000 Structural requirements for intracellular processing and sorting of bactericidal/permeability-increasing protein (BPI): comparison with lipopolysaccharide-binding protein. Journal of leukocyte biology 11 11073106