The bactericidal/permeability-increasing protein (BPI), a potent element in host-defense against gram-negative bacteria and lipopolysaccharide.
The bactericidal/permeability-increasing protein (BPI), is a ca. 55 kDa cytotoxic cationic protein of polymorphonuclear leukocytes (PMN) that is present principally in the azurophilic granules. BPI is toxic only toward Gram-negative bacteria. This target specificity is attributable to the strong attraction of BPI for the lipopolysaccharides (LPS) in the bacterial envelope. BPI also binds with high affinity (apparent Kd 2-5 nM) to a broad range of LPS species and potently inhibits the biologic activities of LPS in vitro. A proteolytically prepared or recombinant ca 25 kDa N-terminal fragment of BPI carries all the antibacterial activities of holo-BPI and is more potent than the holo-protein against more resistant bacteria with S-form LPS in their envelope. The fragment is as active as holo-BPI as an LPS-neutralizing agent in vitro and more potently inhibits cytokine induction by S-form Escherichia coli in whole blood ex vivo. Recombinant forms of both proteins protect animals against the lethal effects of administered LPS.
Elsbach
P
P
Department of Medicine and Microbiology, New York University School of Medicine, New York.
Weiss
J
J
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000302:isolation & purification / Q000502:physiology*; D004731:Endotoxins; D006090:Gram-Negative Bacteria / Q000502:physiology; D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009504:Neutrophils / Q000737:chemistry / Q000502:physiology; D010539:Permeability; D010587:Phagocytosis
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D004731:Endotoxins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; C021623:bactericidal permeability increasing protein