Bactericidal permeability-increasing protein

Bactericidal permeability-increasing protein (BPI) is a 456-residue (~50kDa) protein that is part of the innate immune system, coded for in the human by the BPI gene.[1][2] It belongs to the family of lipid-binding serum glycoproteins.

Bactericidal permeability-increasing protein
Identifiers
SymbolBPI
NCBI gene671
HGNC1095
OMIM109195
RefSeqNM_001725
UniProtP17213
Other data
LocusChr. 20 q11.23
Search for
StructuresSwiss-model
DomainsInterPro

Distribution and function

BPI was initially identified in neutrophils, but is found in other tissues including the epithelial lining of mucous membranes.[3] It is an endogenous antibiotic protein with potent killing activity against Gram-negative bacteria. It binds to compounds called lipopolysaccharides produced by Gram-negative bacteria. Lipolysaccharides are potent activators of the immune system; however, BPI at certain concentrations can prevent this activation.

BPI was discovered by Jerrold Weiss and Peter Elsbach at New York University Medical School.

rBPI21

Because lipopolysaccharides are potent inflammatory agents, and the action of antibiotics can result in the release of these compounds, the binding capacity of BPI was explored as a possible means of reducing injury. Xoma Ltd. developed a recombinant 21kDa portion of the BPI molecule called rBPI21, NEUPREX, or opebecan. In a trial, it was found to decrease the mortality of Gram-negative bacterial-induced sepsis.[4] Studies suggest that its binding activity is not the means by which it mediates its protective effect.[5] Studies show biological effects with Gram-positive bacteria[6] and even in infection by the protozoan, Toxoplasma gondii.[7]

The N-terminal portion of murine BPI (199 amino acids) genetically fused to Halobacterium sp. NRC-1 GvpC protein was bound to the surface of gas vesicle nanoparticles (GVNPs) and tested for protective activity using a murine model of endotoxic shock. Depending on the time of delivery and exposure to lethal concentrations of lipopolysaccharide (LPS) and D-galactosamine, the treatment resulted in increased survival and reduced symptoms of inflammation, including inflammatory anemia, recruitment of neutrophils, liver apoptosis as well as increased pro-inflammatory serum cytokine levels. When administered via footpad and before LPS exposure, there was 100% survival of the experimental cohort.[8]

References
  1. "UniProt". www.uniprot.org. Retrieved 11 June 2023.
  2. Elsbach P (July 1998). "The bactericidal/permeability-increasing protein (BPI) in antibacterial host defense". Journal of Leukocyte Biology. Wiley-Liss. 64 (1): 14–8. doi:10.1002/jlb.64.1.14. PMID 9665269. S2CID 36780757.
  3. Canny G, Levy O, Furuta GT, Narravula-Alipati S, Sisson RB, Serhan CN, Colgan SP (March 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. National Academy of Sciences. 99 (6): 3902–7. Bibcode:2002PNAS...99.3902C. doi:10.1073/pnas.052533799. PMC 122621. PMID 11891303.
  4. Levin M, Quint PA, Goldstein B, Barton P, Bradley JS, Shemie SD, Yeh T, Kim SS, Cafaro DP, Scannon PJ, Giroir BP (September 2000). "Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. rBPI21 Meningococcal Sepsis Study Group". Lancet. Lancet Publishing Group. 356 (9234): 961–7. doi:10.1016/S0140-6736(00)02712-4. PMID 11041396. S2CID 40877544.
  5. Schlag G, Redl H, Davies J, Scannon P (February 1999). "Protective effect of bactericidal/permeability-increasing protein (rBPI21) in baboon sepsis is related to its antibacterial, not antiendotoxin, properties". Annals of Surgery. Lippincott Williams & Wilkins. 229 (2): 262–71. doi:10.1097/00000658-199902000-00015. PMC 1191640. PMID 10024109.
  6. Srivastava A, Casey H, Johnson N, Levy O, Malley R (January 2007). "Recombinant bactericidal/permeability-increasing protein rBPI21 protects against pneumococcal disease". Infection and Immunity. American Society for Microbiology. 75 (1): 342–9. doi:10.1128/IAI.01089-06. PMC 1828387. PMID 17101667.
  7. Khan AA, Lambert LH, Remington JS, Araujo FG (April 1999). "Recombinant bactericidal/permeability-increasing protein (rBPI21) in combination with sulfadiazine is active against Toxoplasma gondii". Antimicrobial Agents and Chemotherapy. American Society for Microbiology. 43 (4): 758–62. doi:10.1128/aac.43.4.758. PMC 89203. PMID 10103177.
  8. Balakrishnan A, DasSarma P, Bhattacharjee O, Kim JM, DasSarma S, Chakravortty D (September 2016). "Halobacterial nano vesicles displaying murine bactericidal permeability-increasing protein rescue mice from lethal endotoxic shock". Scientific Reports. 6: 33679. Bibcode:2016NatSR...633679B. doi:10.1038/srep33679. PMC 5028748. PMID 27646594.
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