Bactericidal permeability-increasing protein

BPI was initially identified in neutrophils, but is found in other tissues including the epithelial lining of mucous membranes.{{cite journal | vauthors = Canny G, Levy O, Furuta GT, Narravula-Alipati S, Sisson RB, Serhan CN, Colgan SP | title = Lipid mediator-induced expression of bactericidal/ permeability-increasing protein (BPI) in human mucosal epithelia | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 6 | pages = 3902–7 | date = March 2002 | pmid = 11891303 | pmc = 122621 | doi = 10.1073/pnas.052533799 | publisher = National Academy of Sciences | bibcode = 2002PNAS...99.3902C | doi-access = free }}

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.

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.{{cite journal | vauthors = Levin M, Quint PA, Goldstein B, Barton P, Bradley JS, Shemie SD, Yeh T, Kim SS, Cafaro DP, Scannon PJ, Giroir BP | title = Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. rBPI21 Meningococcal Sepsis Study Group | journal = Lancet | volume = 356 | issue = 9234 | pages = 961–7 | date = September 2000 | pmid = 11041396 | doi = 10.1016/S0140-6736(00)02712-4 | publisher = Lancet Publishing Group | s2cid = 40877544}} Studies suggest that its binding activity is not the means by which it mediates its protective effect.{{cite journal | vauthors = Schlag G, Redl H, Davies J, Scannon P | title = Protective effect of bactericidal/permeability-increasing protein (rBPI21) in baboon sepsis is related to its antibacterial, not antiendotoxin, properties | journal = Annals of Surgery | volume = 229 | issue = 2 | pages = 262–71 | date = February 1999 | pmid = 10024109 | pmc = 1191640 | doi = 10.1097/00000658-199902000-00015 | publisher = Lippincott Williams & Wilkins }} Studies show biological effects with Gram-positive bacteria{{cite journal | vauthors = Srivastava A, Casey H, Johnson N, Levy O, Malley R | title = Recombinant bactericidal/permeability-increasing protein rBPI21 protects against pneumococcal disease | journal = Infection and Immunity | volume = 75 | issue = 1 | pages = 342–9 | date = January 2007 | pmid = 17101667 | pmc = 1828387 | doi = 10.1128/IAI.01089-06 | publisher = American Society for Microbiology }} and even in infection by the protozoan, Toxoplasma gondii.{{cite journal | vauthors = Khan AA, Lambert LH, Remington JS, Araujo FG | title = Recombinant bactericidal/permeability-increasing protein (rBPI21) in combination with sulfadiazine is active against Toxoplasma gondii | journal = Antimicrobial Agents and Chemotherapy | volume = 43 | issue = 4 | pages = 758–62 | date = April 1999 | pmid = 10103177 | pmc = 89203 | url = | publisher = American Society for Microbiology | doi=10.1128/aac.43.4.758}}

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.{{cite journal | vauthors = Balakrishnan A, DasSarma P, Bhattacharjee O, Kim JM, DasSarma S, Chakravortty D | title = Halobacterial nano vesicles displaying murine bactericidal permeability-increasing protein rescue mice from lethal endotoxic shock | journal = Scientific Reports | volume = 6 | pages = 33679 | date = September 2016 | pmid = 27646594 | pmc = 5028748 | doi = 10.1038/srep33679 | bibcode = 2016NatSR...633679B }}

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