Bactericidal/permeability-increasing protein

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bactericidal/permeability-increasing protein
Identifiers
SymbolBPI
NCBI gene671
HGNC1095
OMIM109195
RefSeqNM_001725
UniProtP17213
Other data
LocusChr. 20 q11.23

Bactericidal/permeability-increasing protein (BPI) is a 456-residue (~50kDa) protein that is part of the innate immune system.[1] It belongs to family of lipid-binding serum glycoproteins.

Distribution and function[]

BPI was initially identified in neutrophils, but is found in other tissues including the epithelial lining of mucous membranes.[2] 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. 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.[3] Studies suggest that its binding activity is not the means by which it mediates its protective effect.[4] Studies show biological effects with Gram-positive bacteria[5] and even in infection by the protozoan, Toxoplasma gondii.[6]

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.[7]

References[]

  1. ^ 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.
  2. ^ 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.
  3. ^ 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. Lay summaryBusiness Wire (2000-09-14). {{cite journal}}: Cite uses deprecated parameter |lay-source= (help)
  4. ^ 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.
  5. ^ 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.
  6. ^ 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.
  7. ^ 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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