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Bactericidal/Permeability-Increasing Protein (BPI): Structure, Function, and Clinical Applications

  • B. P. Giroir
  • S. F. Carroll
  • P. J. Scannon
Part of the Yearbook of Intensive Care and Emergency Medicine book series (YEARBOOK, volume 1998)

Abstract

Bactericidal/permeability-increasing protein (BPI) is a basic protein found in the azurophilic granules of neutrophils, which has multiple anti-infective properties. BPI was first described by Weiss and Elsbach in the mid-1970s as a cationic protein fraction from rabbit polymorphonuclear leukocytes which had potent bactericidal activity against Gram-negative bacteria and which bound bacterial lipopolysaccharides (LPS or endotoxin) [1,2]. Since then, BPI has been cloned and characterized, and genetically engineered fragments of the native molecule have been generated. Additional bioactivities of BPI and proteins derived from its N-terminal domain have been discovered. After 20 years of research and development, bioactive BPI N-terminal protein is now undergoing clinical trials for multiple indications. The purpose of this review is to summarize information relating to the structure of BPI, its activity in vitro, in animal models and in humans, as well as its current clinical development.

Keywords

Cystic Fibrosis Patient Neisseria Meningitidis Major Liver Resection Endotoxin Challenge Intact Bacterium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Weiss J, Elsbach P, Olsson I, Odeberg H (1978) Purification and characterization of a potent bactericidal and membrane active protein from the granules of human polymorphonuclear leukocytes. J Biol Chem 253. 8: 2664–2672Google Scholar
  2. 2.
    Weiss J, Olsson I (1987) Cellular and subcellular localization of the bactericidal/permeability- increasing protein of neutrophils. Blood 69: 652–659PubMedGoogle Scholar
  3. 3.
    Gray PW, Corcorran AE, Eddy RL, Byers MG,Shows TB (1993) The genes for the lipopolysaccha- ride binding protein (LPB) and the bactericidal/permeability-increasing protein (BPI) are encoded in the same region of human chromosome 20. Genomics 15: 188–190Google Scholar
  4. 4.
    Beamer LJ, Carroll SF, Eisenberg D (1997) Crystal structure of human BPI and two bound phospholipids at 2.4 Angstrom resolution. Science 276: 1861–1864PubMedCrossRefGoogle Scholar
  5. 5.
    Ooi CE, Weiss J, Elsbach P, Frangione B, Mannion B (1987) A25-kDa NH2-terminal fragment carries all the antibacterial activities of the human neutrophil 60-kDa bactericidal/permeability-increasing protein. J Biol Chem 262: 14891–14894PubMedGoogle Scholar
  6. 6.
    Appelmelk BJ, An Y-Q, Thijs BG, MacLaren DM, De Graaff J (1994) Recombinant human bactericidal/permeability-increasing protein (rBPI21) is a universal lipopolysaccharide-binding ligand. Infect Immun 62: 3564–3567PubMedGoogle Scholar
  7. 7.
    Capodici C, Chen S, Sidorczyk Z, Elsbach P, Weiss J (1994) Effect of lipopolysaccharide (LPS) chain length on interactions of bactericidal/permeability-increasing protein and its bioactive 23-Kilodalton NH2-Terminal fragment with isolated LPS and intact proteus mirabilis and Escherichia coli. Infect Immun 62: 259–265PubMedGoogle Scholar
  8. 8.
    Weiss J, Elsbach P, Shu C, et al (1992) Human bactericidal/permeability-increasing protein and a recombinant NH2-Terminal fragment cause killing of serum-resistant gram-negative bacteria in whole blood and inhibit tumor necrosis factor release induced by the bacteria. J Clin Invest 90: 1122–1130PubMedCrossRefGoogle Scholar
  9. 9.
    Veld GI, Mannion B, Weiss J, Elsbach P (1988) Effects of the bactericidal/permeability-increasing protein of polymorphonuclear leukocytes on isolated bacterial cytoplasmic membrane vesicles. Infect Immun 56: 1203–1208Google Scholar
  10. 10.
    Levy O, Ooi CE, Weiss J, Lehrer RI, Elsbach P (1994) Individual and synergistic effects of rabbit granulocyte proteins on Escherichia coli. J Clin Invest 94: 672–682PubMedCrossRefGoogle Scholar
  11. 11.
    Marra MN, Wilde CG, Griffithe JE (1990) Bactericidal/permeability-increasing protein has endotoxin-neutralizing activity. J Immunol 144: 662–666PubMedGoogle Scholar
  12. 12.
    Ulevitch RJ, Tobias PS (1995) Receptor-dependent mechanisms of cell stimulation by bacterial endotoxin. Annu Rev Immunol 13: 437–457PubMedCrossRefGoogle Scholar
  13. 13.
    Gazzano-Santoro H, Meszaros K, Birr C, et al (1994) Competition between rBPI23, a recombinant fragment of bactericidal/permeability-increasing protein, and lipopolysaccharide (LPS)-binding protein for binding to LPS and gram-negative bacteria. Infect Immun 62: 1185–1191PubMedGoogle Scholar
  14. 14.
    Katz SS, Chen K, Doerfler ME, Elsbach P, Weiss J (1996) Potent CD14-mediated signalling of human leukocytes by Escherichia coli can be mediated by interaction of whole bacteria and host cells without extensive prior release of endotoxin. Infect Immun 64: 3592–3600PubMedGoogle Scholar
  15. 15.
    Huang K, Fishwild DM, Wu H-M, Dedrick R (1995) Lipopolysaccharide-induced E-selectin expression requires continuous presence of LPS and is inhibited by bactericidal/permeability-increasing protein. Inflammation 19: 389–404PubMedCrossRefGoogle Scholar
  16. 16.
    Corradin SB, Heumann D, Gallay P, Smith J, Mauel J, Glauser MP (1994) Bactericidal/permeability-increasing protein inhibits induction of macrophage nitric oxide production by lipopolysaccharide. J Infect Dis 169: 105–111PubMedCrossRefGoogle Scholar
  17. 17.
    Meszaros K, Parent JB, Gazzano-Santoro H, et al (1993) A recombinant amino terminal fragment of bactericidal/permeability-increasing protein inhibits the induction of leukocyte responses by LPS. J Leukocyte Biol 54: 558–563PubMedGoogle Scholar
  18. 18.
    Arditi M, Zhou J, Huang SH, Luckett PM, Marra MN, Kim KS (1994) Bactericidal/permeability-increasing protein protects vascular endothelial cells from lipopolysaccharide-induced activation and injury. Infect Immun 62: 3930–3936PubMedGoogle Scholar
  19. 19.
    Dedrick R, Conlon PJ (1995) Prolonged expression of lipopolysaccharide (LPS)-induced inflammatory genes in whole blood requires continual exposure to LPS. Infect Immun 63: 1362–1368PubMedGoogle Scholar
  20. 20.
    Fisher CJ, Marra MN, Palardy JE, Marchbanks CR, Scott RW, Opal SM (1994) Human neutrophil bactericidal/permeability-increasing protein reduces mortality from endotoxin challenge: a placebo-controlled study. Crit Care Med 22: 553–558PubMedCrossRefGoogle Scholar
  21. 21.
    Lin Y, Kohn FR, Kung AHC, Ammons WS (1994) Protective effect of a recombinant fragment of bactericidal/permeability increasing protein against carbohydrate dyshomeostasis and tumor necrosis factor-a elevation in rat endotoxemia. Biochem Pharmacol 47: 1553–1559PubMedCrossRefGoogle Scholar
  22. 22.
    Ammons WS, Kung AHC (1993) Recombinant amino terminal fragment of bactericidal/permeability-increasing protein prevents hemodynamic responses to endotoxin. Circ Shock 41: 176–184PubMedGoogle Scholar
  23. 23.
    Vandermeer TJ, Menconi MJ, O’Sullivan BP, et al (1994) Bactericidal/permeability-increasing protein ameliorates acute lung injury in porcine endotoxema. J Appl Physiol 76: 2006–2014PubMedGoogle Scholar
  24. 24.
    Marra MN, Thornton MB, Snable JL, Wilde CG, Scott RW (1994) Endotoxin-binding and -neutralizing properties of recombinant bactericidal/permeability-increasing protein and mono-clonal antibodies HA-1A and E5. Crit Care Med 22: 559–565PubMedCrossRefGoogle Scholar
  25. 25.
    Ammons WS, Kohn FR, Kung AHC (1994) Protective effects of an N-terminal fragment of bactericidal/permeability-increasing protein in rodent models of gram-negative sepsis: Role of bactericidal properties. J Infect Dis 170: 1473–1482PubMedCrossRefGoogle Scholar
  26. 26.
    Opal SM, Palardy JE, Jhung JW, et al (1995) Activity of lipopolysaccharide-binding protein-bactericidal/permeability-increasing protein fusion peptide in an experimental model of Pseudomonas sepsis. Antimicrob Agents Chemother 39: 2813–2815PubMedGoogle Scholar
  27. 27.
    Lechner AJ, Lamprech KE, Johanns CA, Matuschak GM (1995) The recombinant 23-kDa N-terminal fragment of bactericidal/permeability-increasing protein (rBPI-23) decreases Escheri-chia coli-induced mortality and organ injury during immunosuppression-related neutropenia. Shock 4: 298–306PubMedCrossRefGoogle Scholar
  28. 28.
    Lin Y, Leach WJ, Ammons WS (1996) Synergistic effect of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein and cefamandole in treatment of rabbit gram- negative sepsis. Antimicrob Agents Chemother 40: 65–69PubMedGoogle Scholar
  29. 29.
    Rogy MA, Oldenburg HS A, Calvano SE, et al (1994) The Role of bactericidal/permeability- increasing protein in the treatment of primate bacteremia and septic shock. J Clin Immunol 14: 120–133PubMedCrossRefGoogle Scholar
  30. 30.
    Rogy MA, Moldawer LL, Oldenburg HSA, et al (1994) Anti-endotoxin therapy in primate bacteremia with HA-1A and BPI. Ann Surg 220: 77–85PubMedCrossRefGoogle Scholar
  31. 31.
    Bauer RJ, White ML, Nelson BJ, et al (1996) A phase I safety and pharmacokinetic study of a recombinant amino terminal fragment of bactericidal/permeability-increasing protein in healthy male volunteers. Shock 5: 91–96PubMedCrossRefGoogle Scholar
  32. 32.
    von der Mohlen MAM, Kimmings AK, Wedel NI, et al (1995) Inhibition of endotoxin-induced cytokine release and neutrophil activation in humans by use of recombinant bactericidal/permeability-increasing protein. J Infect Dis 172: 144–151PubMedCrossRefGoogle Scholar
  33. 33.
    Wong HR, Doughty LA, Wedel N, et al (1995) Plasma bactericidal/permeability-increasing protein concentrations in critically ill children with the sepsis syndrome. Pediatr Infect Dis J 14: 1087–1091PubMedCrossRefGoogle Scholar
  34. 34.
    Calvano SE, Thompson WA, Marra MN, et al (1994) Changes in polymorphonuclear leukocyte surface and plasma bactericidal/permeability-increasing protein and plasma lipopolysaccharide binding protein during endotoxemia or sepsis. Arch Surg 129: 220–226PubMedCrossRefGoogle Scholar
  35. 35.
    Giroir BP, Quint PA, Barton P, et al (1997) Preliminary evaluation of recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in children with severe meningococcal disease. Lancet 350: 1439–1443PubMedCrossRefGoogle Scholar
  36. 36.
    Yao YM, Bahrami S, Leichtfried G,Redl H, Schlag G (1995) Pathogenesis of hemorrhage-induced bacteria/endotoxin translocation in rats. Ann Surg 221: 398–405Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • B. P. Giroir
  • S. F. Carroll
  • P. J. Scannon

There are no affiliations available

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