Bactericidal Permeability-Increasing Protein in Host Defence Against Gram-negative Bacteria and Endotoxin

  1. Joan Marsh Organizer and
  2. Jamie A. Goode
  1. Peter Elsbach

Published Online: 28 SEP 2007

DOI: 10.1002/9780470514658.ch11

Ciba Foundation Symposium 186 - Antimicrobial Peptides

Ciba Foundation Symposium 186 - Antimicrobial Peptides

How to Cite

Elsbach, P. (2007) Bactericidal Permeability-Increasing Protein in Host Defence Against Gram-negative Bacteria and Endotoxin, in Ciba Foundation Symposium 186 - Antimicrobial Peptides (eds J. Marsh and J. A. Goode), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470514658.ch11

Author Information

  1. Department of Medicine, New York University Medical Center, New York, NY 10016, USA

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471950257

Online ISBN: 9780470514658

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Keywords:

  • bactericidal permeability;
  • host defence;
  • gram-negative bacteria;
  • endotoxin;
  • biological effects

Summary

The bactericidal permeability-increasing protein (BPI) is a highly conserved host-defence molecule produced and stored by myeloid cells only and a major constituent of the primary granules of human and rabbit polymorphonuclear leukocytes. The c. 50 kDa BPI and a c. 23 kDa bioactive N-terminal fragment are cytotoxic only for Gram-negative bacteria. This target-cell specificity reflects the high affinity (apparent Kd: 1–10nM) of BPI for the lipid A portion of lipopolysaccharide (LPS or endotoxin). Native and recombinant (r) holo-BPI and the N-terminal fragment (rBPI-23) bind with equal affinity to all forms of isolated LPS examined and inhibit the numerous biological effects of LPS in vitro (including in whole blood ex vivo) as well as in animals. Under the same conditions the anti-bacterial potencies of holo-BPI and rBPI-23 against Gram-negative bacteria with rough chemotype LPS (whether encapsulated or not) are also the same, but against more resistant smooth chemotype Gram-negative bacteria rBPI-23 is up to 30-fold more potent than holo-BPI. Holo-BPI and rBPI-23 protect a broad range of animals against lethal cytotoxic effects of LPS and in some cases against lethal inoculations with live Gram-negative bacteria.