title: Bactericidal permeability-increasing protein in host defence against gram-negative bacteria and endotoxin.
abstract: 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: 1-10 nM) 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 antibacterial 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.
authors.affiliation: Department of Medicine, New York University Medical Center, New York 10016, USA.
authors.forename: P
authors.initials: P
authors.lastname: Elsbach
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000737:chemistry / Q000494:pharmacology*; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D008565:Membrane Proteins; D009504:Neutrophils / Q000276:immunology; D013329:Structure-Activity Relationship
chemical_list: D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D004731:Endotoxins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C021623:bactericidal permeability increasing protein