Bactericidal permeability-increasing protein
| Bactericidal permeability-increasing protein | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | BPI | ||||||
| NCBI gene | 671 | ||||||
| HGNC | 1095 | ||||||
| OMIM | 109195 | ||||||
| RefSeq | NM_001725 | ||||||
| UniProt | P17213 | ||||||
| Other data | |||||||
| Locus | Chr. 20 q11.23 | ||||||
| |||||||
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.
Distribution and function
[edit]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
[edit]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
[edit]- ^ "UniProt". www.uniprot.org. Retrieved 11 June 2023.
- ^ Elsbach P (July 1998). "The bactericidal/permeability-increasing protein (BPI) in antibacterial host defense". Journal of Leukocyte Biology. 64 (1). Wiley-Liss: 14–8. doi:10.1002/jlb.64.1.14. PMID 9665269. S2CID 36780757.
- ^ 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. 99 (6). National Academy of Sciences: 3902–7. Bibcode:2002PNAS...99.3902C. doi:10.1073/pnas.052533799. PMC 122621. PMID 11891303.
- ^ 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. 356 (9234). Lancet Publishing Group: 961–7. doi:10.1016/S0140-6736(00)02712-4. PMID 11041396. S2CID 40877544.
- ^ 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. 229 (2). Lippincott Williams & Wilkins: 262–71. doi:10.1097/00000658-199902000-00015. PMC 1191640. PMID 10024109.
- ^ 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. 75 (1). American Society for Microbiology: 342–9. doi:10.1128/IAI.01089-06. PMC 1828387. PMID 17101667.
- ^ 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. 43 (4). American Society for Microbiology: 758–62. doi:10.1128/aac.43.4.758. PMC 89203. PMID 10103177.
- ^ 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.
External links
[edit]- bactericidal+permeability+increasing+protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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