The role of bactericidal/permeability-increasing protein in the treatment of primate bacteremia and septic shock

The role of bactericidal/permeability-increasing protein in the treatment of primate bacteremia and septic shock

Human neutrophil azurophilic granules contain an approximately 55-kDa protein, known as bactericidal/permeability-increasing protein (BPI), which possesses a high-affinity binding domain for the lipid A component of lipopolysaccharide (LPS). The in vivo LPS neutralizing activity of exogenous BPI was...

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Bibliographic Details
Published in:Journal of clinical immunology Vol. 14; no. 2; pp. 120 - 133
Main Authors: ROGY, M. A, OLDENBURG, H. S. A, LOWRY, S. F, CALVANO, S. E, MONTEGUT, W. J, STACKPOLE, S. A, VAN ZEE, K. J, MARRA, M. N, SCOTT, R. W, SEILHAMMER, J. J, MALDAWER, L. L
Format: Journal Article
Language:English
Published: New York, NY Kluwer/Plenum 01-03-1994
Subjects:
Animals
Anti-Infective Agents - therapeutic use
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimicrobial Cationic Peptides
Bacteremia - therapy
Biological and medical sciences
Blood Proteins - therapeutic use
Escherichia coli Infections - therapy
Interleukin-6 - biosynthesis
Medical sciences
Membrane Proteins
Neutrophils - immunology
Papio
Pharmacology. Drug treatments
Receptors, Tumor Necrosis Factor - metabolism
Recombinant Proteins - therapeutic use
Shock, Septic - therapy
Tumor Necrosis Factor-alpha - biosynthesis
Cell factor
Escherichia coli
Papio anubis
Biological activity
Bacteremia
Bactericidal effect
Infection
Vertebrata
Mammalia
Treatment
Animal
Bacteriosis
Primates
Simioidea
Lipopolysaccharide
Bacteria
Antagonist
Neutrophil
Enterobacteriaceae
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Summary:Human neutrophil azurophilic granules contain an approximately 55-kDa protein, known as bactericidal/permeability-increasing protein (BPI), which possesses a high-affinity binding domain for the lipid A component of lipopolysaccharide (LPS). The in vivo LPS neutralizing activity of exogenous BPI was studied in a model of lethal Escherichia coli bacteremia. Five baboons were treated with BPI (5 mg/kg bolus injection followed by a 95 micrograms/kg/min BPI infusion over 4 hr), while four additional animals received a genetically engineered variant of BPI (NCY103). Five animals received a placebo treatment and served as controls. Both wild-type rhBPI and NCY103 significantly (P < 0.05) decreased blood levels of LPS throughout an 8-hr evaluation period following live bacterial challenge. Two hours following E. coli administration, LPS levels peaked in the controls, at 6.86 +/- 3.22 ng/ml, whereas LPS levels were 3.39 +/- 2.1 ng/ml in the BPI group and 2.04 +/- 1.18 ng/ml in the NCY103 group. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 levels likewise were attenuated in the treatment groups, whereas circulating sTNFR I was significantly (P < 0.05) reduced only in the BPI group. Leukocytopenia and granulocytopenia were significantly (P < 0.02) lessened in the BPI group, by an average of 59% leukocytopenia and 65% granulocytopenia, respectively. This study supports the concept of E. coli LPS neutralization by BPI in vivo and demonstrates that a moderate (70%) reduction in peak LPS-LAL activity is sufficient to alter some hematologic and cytokine manifestations of bacteremia.
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ISSN:0271-9142
1573-2592
DOI:10.1007/BF01541345